全文获取类型
收费全文 | 230篇 |
免费 | 30篇 |
出版年
2023年 | 12篇 |
2022年 | 22篇 |
2021年 | 20篇 |
2020年 | 14篇 |
2019年 | 15篇 |
2018年 | 12篇 |
2017年 | 7篇 |
2016年 | 9篇 |
2015年 | 13篇 |
2014年 | 9篇 |
2013年 | 20篇 |
2012年 | 6篇 |
2011年 | 11篇 |
2010年 | 8篇 |
2009年 | 7篇 |
2008年 | 8篇 |
2007年 | 9篇 |
2006年 | 4篇 |
2005年 | 8篇 |
2004年 | 10篇 |
2003年 | 8篇 |
2002年 | 8篇 |
2001年 | 4篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1998年 | 5篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1993年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
排序方式: 共有260条查询结果,搜索用时 343 毫秒
1.
《Critical reviews in biochemistry and molecular biology》2013,48(5):409-435
Telomere DNA-binding proteins protect the ends of chromosomes in eukaryotes. A subset of these proteins are constructed with one or more OB folds and bind with G+T-rich single-stranded DNA found at the extreme termini. The resulting DNA-OB protein complex interacts with other telomere components to coordinate critical telomere functions of DNA protection and DNA synthesis. While the first crystal and NMR structures readily explained protection of telomere ends, the picture of how single-stranded DNA becomes available to serve as primer and template for synthesis of new telomere DNA is only recently coming into focus. New structures of telomere OB fold proteins alongside insights from genetic and biochemical experiments have made significant contributions towards understanding how protein-binding OB proteins collaborate with DNA-binding OB proteins to recruit telomerase and DNA polymerase for telomere homeostasis. This review surveys telomere OB protein structures alongside highly comparable structures derived from replication protein A (RPA) components, with the goal of providing a molecular context for understanding telomere OB protein evolution and mechanism of action in protection and synthesis of telomere DNA. 相似文献
2.
Arrestins are important scaffolding proteins that are expressed in all vertebrate animals. They regulate cell-signaling events upon binding to active G-protein coupled receptors (GPCR) and trigger endocytosis of active GPCRs. While many of the functional sites on arrestins have been characterized, the question of how these sites interact is unanswered. We used anisotropic network modeling (ANM) together with our covariance compliment techniques to survey all the available structures of the nonvisual arrestins to map how structural changes and protein-binding affect their structural dynamics. We found that activation and clathrin binding have a marked effect on arrestin dynamics, and that these dynamics changes are localized to a small number of distant functional sites. These sites include α-helix 1, the lariat loop, nuclear localization domain, and the C-domain β-sheets on the C-loop side. Our techniques suggest that clathrin binding and/or GPCR activation of arrestin perturb the dynamics of these sites independent of structural changes. 相似文献
3.
4.
《Journal of molecular biology》2021,433(19):167150
The resistance of Gram-negative bacteria to β-lactam antibiotics stems mainly from β-lactamase proteins that hydrolytically deactivate the β-lactams. Of particular concern are the β-lactamases that can deactivate a class of β-lactams known as carbapenems. Carbapenems are among the few anti-infectives that can treat multi-drug resistant bacterial infections. Revealing the mechanisms of their deactivation by β-lactamases is a necessary step for preserving their therapeutic value. Here, we present NMR investigations of OXA-24/40, a carbapenem-hydrolyzing Class D β-lactamase (CHDL) expressed in the gram-negative pathogen, Acinetobacter baumannii. Using rapid data acquisition methods, we were able to study the “real-time” deactivation of the carbapenem known as doripenem by OXA-24/40. Our results indicate that OXA-24/40 has two deactivation mechanisms: canonical hydrolytic cleavage, and a distinct mechanism that produces a β-lactone product that has weak affinity for the OXA-24/40 active site. The mechanisms issue from distinct active site environments poised either for hydrolysis or β-lactone formation. Mutagenesis reveals that R261, a conserved active site arginine, stabilizes the active site environment enabling β-lactone formation. Our results have implications not only for OXA-24/40, but the larger family of CHDLs now challenging clinical settings on a global scale. 相似文献
5.
Burak Erman 《Proteins》2013,81(7):1097-1101
Fluctuations of the distance between a pair of residues i and j may be correlated with the fluctuations of the distance between another pair k and l. In this case, information may be transmitted among these four residues. Allosteric activity is postulated to proceed through such correlated paths. In this short communication a fast method for calculating correlations among all possible pairs ij and kl leading to a pathway of correlated residues of a protein is proposed. The method is based on the alpha carbon centered Gaussian Network Model. The model is applied to Glutamine Amidotransferase and pathways of allosteric activity are identified and compared with literature. Proteins 2013; 81:1097–1101. © 2013 Wiley Periodicals, Inc. 相似文献
6.
Terry A. Gray Euan Murray Matthew W. Nowicki Lucy Remnant Alexander Scherl Petr Muller Borek Vojtesek Ted R. Hupp 《Protein science : a publication of the Protein Society》2013,22(9):1266-1278
Many regulatory proteins are homo‐oligomeric and designing assays that measure self‐assembly will provide novel approaches to study protein allostery and screen for novel small molecule modulators of protein interactions. We present an assay to begin to define the biochemical determinants that regulate dimerization of the cancer‐associated oncoprotein AGR2. A two site‐sandwich microtiter assay (2SMTA) was designed using a DyLight800‐labeled monoclonal antibody that binds to an epitope in AGR2 to screen for synthetic self‐peptides that might regulate dimer stability. Peptides derived from the intrinsically disordered N‐terminal region of AGR2 increase in trans oligomer stability as defined using the 2SMTA assay. A DSS‐crosslinking assay that traps the AGR2 dimer through K95‐K95 adducts confirmed that Δ45‐AGR2 was a more stable dimer using denaturing gel electrophoresis. A titration of wt‐AGR2, Δ45‐AGR2 (more stable dimer), and monomeric AGR2E60A revealed that Δ45‐AGR2 was more active in binding to Reptin than either wt‐AGR2 or the AGR2E60A mutant. Our data have defined a functional role for the AGR2 dimer in the binding to its most well characterized interacting protein, Reptin. The ability to regulate AGR2 oligomerization in trans opens the possibility for developing small molecules that regulate its' biochemical activity as potential cancer therapeutics. The data also highlight the utility of this oligomerization assay to screen chemical libraries for ligands that could regulate AGR2 dimer stability and its' oncogenic potential. 相似文献
7.
Javier Oroz Laura J. Blair Markus Zweckstetter 《Protein science : a publication of the Protein Society》2019,28(9):1545-1551
Hsp90 is an essential chaperone that requires large allosteric changes to determine its ATPase activity and client binding. The co‐chaperone Aha1, which is the major ATPase stimulator in eukaryotes, is important for regulation of Hsp90's allosteric timing. Little is known, however, about the structure of the Hsp90/Aha1 complex. Here, we characterize the solution structure of unmodified human Hsp90/Aha1 complex using NMR spectroscopy. We show that the 214‐kDa complex forms by a two‐step binding mechanism and adopts multiple conformations in the absence of nucleotide. Aha1 induces structural changes near Hsp90's nucleotide‐binding site, providing a basis for its ATPase‐enhancing activity. Our data reveal important aspects of this pivotal chaperone/co‐chaperone interaction and emphasize the relevance of characterizing dynamic chaperone structures in solution. 相似文献
8.
9.
10.
《Structure (London, England : 1993)》2019,27(8):1308-1315.e3