全文获取类型
收费全文 | 1608篇 |
免费 | 149篇 |
专业分类
1757篇 |
出版年
2023年 | 18篇 |
2022年 | 29篇 |
2021年 | 52篇 |
2020年 | 49篇 |
2019年 | 54篇 |
2018年 | 40篇 |
2017年 | 39篇 |
2016年 | 74篇 |
2015年 | 132篇 |
2014年 | 112篇 |
2013年 | 120篇 |
2012年 | 165篇 |
2011年 | 141篇 |
2010年 | 78篇 |
2009年 | 61篇 |
2008年 | 84篇 |
2007年 | 70篇 |
2006年 | 66篇 |
2005年 | 50篇 |
2004年 | 48篇 |
2003年 | 27篇 |
2002年 | 37篇 |
2001年 | 15篇 |
2000年 | 7篇 |
1999年 | 13篇 |
1998年 | 6篇 |
1997年 | 6篇 |
1995年 | 9篇 |
1993年 | 5篇 |
1992年 | 8篇 |
1990年 | 6篇 |
1989年 | 4篇 |
1988年 | 8篇 |
1987年 | 10篇 |
1986年 | 7篇 |
1984年 | 4篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 4篇 |
1980年 | 6篇 |
1979年 | 7篇 |
1978年 | 8篇 |
1977年 | 4篇 |
1976年 | 4篇 |
1975年 | 4篇 |
1974年 | 4篇 |
1973年 | 7篇 |
1972年 | 4篇 |
1969年 | 5篇 |
1968年 | 8篇 |
排序方式: 共有1757条查询结果,搜索用时 11 毫秒
11.
Hao Wu Lei Sun Fabian Blombach Stan J.J. Brouns Ambrosius P. L. Snijders Kristina Lorenzen Robert H. H. van den Heuvel Albert J. R. Heck Sheng Fu Xuemei Li Xuejun C. Zhang Zihe Rao John van der Oost 《Proteins》2010,78(3):705-713
The HflX‐family is a widely distributed but poorly characterized family of translation factor‐related guanosine triphosphatases (GTPases) that interact with the large ribosomal subunit. This study describes the crystal structure of HflX from Sulfolobus solfataricus solved to 2.0‐Å resolution in apo‐ and GDP‐bound forms. The enzyme displays a two‐domain architecture with a novel “HflX domain” at the N‐terminus, and a classical G‐domain at the C‐terminus. The HflX domain is composed of a four‐stranded parallel β‐sheet flanked by two α‐helices on either side, and an anti‐parallel coiled coil of two long α‐helices that lead to the G‐domain. The cleft between the two domains accommodates the nucleotide binding site as well as the switch II region, which mediates interactions between the two domains. Conformational changes of the switch regions are therefore anticipated to reposition the HflX‐domain upon GTP‐binding. Slow GTPase activity has been confirmed, with an HflX domain deletion mutant exhibiting a 24‐fold enhanced turnover rate, suggesting a regulatory role for the HflX domain. The conserved positively charged surface patches of the HflX‐domain may mediate interaction with the large ribosomal subunit. The present study provides a structural basis to uncover the functional role of this GTPases family whose function is largely unknown. Proteins 2010. © 2009 Wiley‐Liss, Inc. 相似文献
12.
13.
Angela Brieger Boris Adryan Fabian Wolpert Sandra Passmann Stefan Zeuzem Jörg Trojan 《Proteomics》2010,10(18):3343-3355
The involvement of MLH1 in several mismatch repair‐independent cellular processes has been reported. In an attempt to gain further insight into the protein's cellular functions, we screened for novel interacting partners of MLH1 utilizing a bacterial two‐hybrid system. Numerous unknown interacting proteins were identified, suggesting novel biological roles of MLH1. The network of MLH1 and its partner proteins involves a multitude of cellular processes. Integration of our data with the “General Repository for Interaction Datasets” highlighted that MLH1 exhibits relationships to three interacting pairs of proteins involved in cytoskeletal and filament organization: Thymosin β 4 and Actin γ, Cathepsin B and Annexin A2 as well as Spectrin α and Desmin. Coimmunoprecipitation and colocalization experiments validated the interaction of MLH1 with these proteins. Differential mRNA levels of many of the identified proteins, detected by microarray analysis comparing MLH1‐deficient and ‐proficient cell lines, support the assumed interplay of MLH1 and the identified candidate proteins. By siRNA knock down of MLH1, we demonstrated the functional impact of MLH1–Actin interaction on filament organization and propose that dysregulation of MLH1 plays an essential role in cytoskeleton dynamics. Our data suggest novel roles of MLH1 in cellular organization and colorectal cancerogenesis. 相似文献
14.
15.
16.
Marcin Moch Reinhard Windoffer Nicole Schwarz Raphaela Pohl Andreas Omenzetter Uwe Schnakenberg Fabian Herb Kraisorn Chaisaowong Dorit Merhof Lena Ramms Gloria Fabris Bernd Hoffmann Rudolf Merkel Rudolf E. Leube 《PloS one》2016,11(3)
The keratin intermediate filament cytoskeleton protects epithelial cells against various types of stress and is involved in fundamental cellular processes such as signaling, differentiation and organelle trafficking. These functions rely on the cell type-specific arrangement and plasticity of the keratin system. It has been suggested that these properties are regulated by a complex cycle of assembly and disassembly. The exact mechanisms responsible for the underlying molecular processes, however, have not been clarified. Accumulating evidence implicates the cytolinker plectin in various aspects of the keratin cycle, i.e., by acting as a stabilizing anchor at hemidesmosomal adhesion sites and the nucleus, by affecting keratin bundling and branching and by linkage of keratins to actin filament and microtubule dynamics. In the present study we tested these hypotheses. To this end, plectin was downregulated by shRNA in vulvar carcinoma-derived A431 cells. As expected, integrin β4- and BPAG-1-positive hemidesmosomal structures were strongly reduced and cytosolic actin stress fibers were increased. In addition, integrins α3 and β1 were reduced. The experiments furthermore showed that loss of plectin led to a reduction in keratin filament branch length but did not alter overall mechanical properties as assessed by indentation analyses using atomic force microscopy and by displacement analyses of cytoplasmic superparamagnetic beads using magnetic tweezers. An increase in keratin movement was observed in plectin-depleted cells as was the case in control cells lacking hemidesmosome-like structures. Yet, keratin turnover was not significantly affected. We conclude that plectin alone is not needed for keratin assembly and disassembly and that other mechanisms exist to guarantee proper keratin cycling under steady state conditions in cultured single cells. 相似文献
17.
18.
Bruce D. Davies Wayne Hoss Jan-Ping Lin Fabian Lionetti 《Molecular and cellular biochemistry》1982,44(1):23-31
Summary A noncholinergic nicotine receptor on human phagocytic leukocytes has been characterized using the binding of3H-(d,l)-nicotine. The average affinity +/-standard deviation of (d,l)-nicotine for the receptor on neutrophils is 36 ± 18 nM (n=6). The binding is saturable with an average of 8.7 x 104 sites per neutrophil. Monocytes and to a lesser extent lymphocytes but not erythrocytes also display specific binding. Bound nicotine is dissociable from the receptor and is not metabolized. Only close structural analogs of nicotine bind to the receptor, which is stereoselective for the (d)-isomer. The receptor can be occupied by (l)-nicotine at concentrations present in the blood of smokers. It is suggested that some of the adverse effects of smoking on leukocyte functions may be mediated by a specific nicotine receptor. 相似文献
19.
20.