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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
51

Transcriptional regulation of receptor tyrosine kinases AXL and MER in the testis /

Wong, Chui-shan. January 2005 (has links)
Thesis (Ph. D.)--University of Hong Kong, 2005.
52

Analysis of ErbB receptors regulation of ErbB-1 kinase activation and localization of ErbB-4 to membrane microdomains /

Thiel, Kristina Wyatt. January 2007 (has links)
Thesis (Ph. D. in Biochemistry)--Vanderbilt University, Dec. 2007. / Title from title screen. Includes bibliographical references.
53

Quantitative imaging of tyrosine kinase-drug interactions in cells.

Chuntharpursat, Eulashini. January 2012 (has links)
Kinases play a crucial role in regulating cellular signaling cascades, making them therapeutic targets for several human diseases. In human cancers, mis-regulation and mutations of kinases such as EGFR (epidermal growth factor receptor) have been found to drive malignant transformation. Due to the conserved structural elements of protein kinases, the majority of kinase inhibitors available have a tendency to inhibit multiple targets. The biological impact of this promiscuity is insufficiently defined and the prevalence of cellular compensatory mechanisms additionally varies the clinical responses to drug treatment. In order to understand the relationship between selectivity and efficacy, prior to clinical trials, it is essential to characterize how inhibitors interact with the kinome within a cellular context. Monitoring inhibitor-target interactions generally involves in vitro assaying with purified proteins or protein domains, which compromises the native integrity of the kinases. Cellbased assays either gain outcomes from bulk populations that average out cell variance or phenotypic assays that lack molecular resolution. To obtain information on drug interactions on a single cell level, we have developed a method to measure the direct binding of kinase inhibitors to their targets in situ and in vivo. Kinase inhibitors are chemically tagged with fluorophores that serve as acceptors to genetically tagged donor fluorophores on the enzyme and the interaction is measured using FRET-FLIM. With epidermal growth factor receptor (EGFR) and irreversible EGFR inhibitors as the model system, this approach has been applied to image inhibitor-kinase interactions in live and fixed cells. Using this method, a small panel of tyrosine kinase targets, and labeled inhibitors, we were able to investigate the cross-specificity within the panel. Additionally it was found that the specificity of inhibitors for specific kinase conformations enables the distinction between EGFR in the active and inactive conformation by the inhibitor-probes. / Thesis (Ph.D.)-University of KwaZulu-Natal, Pietermaritzburg, 2011.
54

Molecular dissection of B-lymphocyte signalling using expression profiling /

Lindvall, Jessica M., January 2005 (has links)
Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.
55

The significance of proline rich tyrosine kinase 2 (PYK2) in proliferation and invasiveness of hepatocellular carcinoma

Sun, Kin-wai., 孫建維. January 2008 (has links)
published_or_final_version / Surgery / Doctoral / Doctor of Philosophy
56

Role of RON activation on chemoresistance in gastric cancer

Tse, Tak-fong., 謝德芳. January 2007 (has links)
published_or_final_version / abstract / Surgery / Master / Master of Philosophy
57

Gene regulation of zebrafish hematopoiesis during embryonic development with special references to survivins and jak2a

Ma, Chun-hang., 馬進恆. January 2009 (has links)
published_or_final_version / Medicine / Doctoral / Doctor of Philosophy
58

Investigations of ephrin ligands during development

Tosch, Paul. January 2002 (has links) (PDF)
"May 2002." Addendum inside back cover. Bibliography: p. 139-157. Aims to isolate ephrin ligands from Drosophila melanogaster and analyse their involvement in Drosophila deveopment. Also investigates the potential of ephrin B-1 as a causative gene in the human condition Aicardi's syndrome.
59

Investigations of ephrin ligands during development / by Paul Tosch.

Tosch, Paul January 2002 (has links)
"May 2002." / Addendum inside back cover. / Bibliography: p. 139-157. / 174 p. : ill. (some col.), col. plates ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Aims to isolate ephrin ligands from Drosophila melanogaster and analyse their involvement in Drosophila deveopment. Also investigates the potential of ephrin B-1 as a causative gene in the human condition Aicardi's syndrome. / Thesis (Ph.D.)--University of Adelaide, Dept. of Molecular Biosciences, 2003
60

Development of small-molecule ligands for SH3 protein domains.

Inglis, Steven Robert January 2005 (has links)
Src Homology 3 (SH3) domains are small protein- protein interaction domains that bind to proline-rich peptides, mediating a range of important biological processes. Because the deregulation of events involving SH3 domains forms the basis of many human diseases, the SH3 domains are appealing targets for the development of potential therapeutics. Previously in the field, no examples of entirely small-molecule ligands for the SH3 domains have been identified. However, in our research group, we have discovered a class of heterocyclic compounds that bind to the Tec SH3 domain at conserved residues in the proline-rich peptide binding site, with weak to moderate affinity. The highest affinity of these was 2- aminoquinoline (Kd = 125 mM). In this thesis, a range of approaches are described, that were intended to contribute towards development of higher affinity small-molecule ligands for the Tec SH3 domain. Preliminary experiments, involving testing a variety of compounds structurally related to 2- aminoquinoline, provided new structure activity information, and led to a better understanding of the 2-aminoquinoline/SH3 domain binding event. The major component of this thesis is a thorough investigation into the synthesis of a range of 2- aminoquinoline derivatives. N-Substituted- 2-aminoquinolines were synthesised, however these compounds bound the SH3 domain with slightly lower affinity than 2-aminoquinoline. 6- Substituted-2-aminoquinolines were subsequently prepared, and ligands were identified with up to six-fold improved affinity relative to 2-aminoquinoline, and enhanced selectivity for the Tec SH3 domain. The techniques used for the ligand binding studies were Nuclear Magnetic Resonance (NMR) chemical shift perturbation and Fluorescence Polarisation (FP) peptide displacement assays. As part of the ligand binding studies, it was intended that the 3D tructure of a 2- aminoquinoline ligand/SH3 complex would be obtained using NMR methods, provided that a ligand was identified that bound the SH3 domain in slow exchange on the NMR timescale. However, this goal was not fulfilled. Despite this, the work presented in this thesis provides a solid foundation for the development of potent 2-aminoquinoline ligands for SH3 domains, with engineered specificity. / Thesis (Ph.D.)--School of Molecular and Biomedical Science, 2005.

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