全文获取类型
收费全文 | 862篇 |
免费 | 55篇 |
出版年
2023年 | 11篇 |
2022年 | 7篇 |
2021年 | 28篇 |
2020年 | 11篇 |
2019年 | 28篇 |
2018年 | 27篇 |
2017年 | 17篇 |
2016年 | 30篇 |
2015年 | 36篇 |
2014年 | 50篇 |
2013年 | 53篇 |
2012年 | 76篇 |
2011年 | 78篇 |
2010年 | 53篇 |
2009年 | 56篇 |
2008年 | 72篇 |
2007年 | 62篇 |
2006年 | 53篇 |
2005年 | 42篇 |
2004年 | 30篇 |
2003年 | 34篇 |
2002年 | 27篇 |
2001年 | 5篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 3篇 |
1997年 | 5篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1990年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1983年 | 3篇 |
1953年 | 1篇 |
排序方式: 共有917条查询结果,搜索用时 187 毫秒
911.
Katerina Zabrady Marek Adamus Lucie Vondrova Chunyan Liao Hana Skoupilova Marketa Novakova Lenka Jurcisinova Aaron Alt Antony W. Oliver Alan R. Lehmann Jan J. Palecek 《Nucleic acids research》2016,44(3):1064-1079
SMC5/6 is a highly conserved protein complex related to cohesin and condensin, which are the key components of higher-order chromatin structures. The SMC5/6 complex is essential for proliferation in yeast and is involved in replication fork stability and processing. However, the precise mechanism of action of SMC5/6 is not known. Here we present evidence that the NSE1/NSE3/NSE4 sub-complex of SMC5/6 binds to double-stranded DNA without any preference for DNA-replication/recombination intermediates. Mutations of key basic residues within the NSE1/NSE3/NSE4 DNA-binding surface reduce binding to DNA in vitro. Their introduction into the Schizosaccharomyces pombe genome results in cell death or hypersensitivity to DNA damaging agents. Chromatin immunoprecipitation analysis of the hypomorphic nse3 DNA-binding mutant shows a reduced association of fission yeast SMC5/6 with chromatin. Based on our results, we propose a model for loading of the SMC5/6 complex onto the chromatin. 相似文献
912.
Petr Lapcik Barbora Vesela David Potesil Katerina Dadakova Martina Zapletalova Petr Benes Pavel Bouchal Eva Matalova 《Proteomics》2023,23(11):2200408
Caspase-9 is the major apical caspase responsible for triggering the intrinsic apoptotic pathway. Our previous study indicated that specific inhibition of caspase-9 caused microscopically evident alterations in appearance of the primary chondrogenic cultures which cannot be explained by decrease in apoptosis. To describe a complex molecular background of this effect, proteomics analysis of control and caspase-9 inhibitor-treated chondrogenic cultures were performed. Proteins were extracted, identified and quantified using LC-MS in both data dependent and data independent acquisition (DIA) mode. While directDIA analysis of diaPASEF data obtained using timsTOF Pro LC-MS system revealed 7849 protein groups (Q-value <0.01), a parallel analysis of iTRAQ-2DLC-MS3 and conventional DIA-MS data identified only 5146 and 4098 protein groups, respectively, showing diaPASEF a superior method for the study. The detailed analysis of diaPASEF data disclosed 236/551 significantly down-/up-regulated protein groups after caspase-9 inhibition, respectively (|log2FC|>0.58, Q value <0.05). Classification of downregulated proteins revealed changes in extracellular matrix organization, collagen metabolism, and muscle system processes. Moreover, deregulations suggest a switch from glycolytic to lipid based metabolism in the inhibited cells. No essential changes were found in the proteins involved in apoptosis. The data indicate new non-apoptotic participation of caspases in chondrocyte homeostasis with potential applications in cartilage pathophysiology. 相似文献
913.
Magdalena Niedziakowska Karolina Doan Marcin Grny Maciej Sykut Krzysztof Stefaniak Natalia Piotrowska Bogumia Jdrzejewska Bogdan Ridush Sawomira Paweczyk Pawe Mackiewicz Ulrich Schmlcke Pavel Kosintsev Daniel Makowiecki Maxim Charniauski Dariusz Krasnodbski Eve Ranname Urmas Saarma Marine Arakelyan Ninna Manaseryan Vadim V. Titov Pavel Hulva Adrian Blescu Ralph Fyfe Jessie Woodbridge Katerina Trantalidou Vesna Dimitrijevi Oleksandr Kovalchuk Jarosaw Wilczyski Theodor Obad Grzegorz Lipecki Alesia Arabey Ana Stankovi 《Journal of Biogeography》2021,48(1):147-159
914.
Sergey V. Abkin Katerina M. Pankratova Elena Yu. Komarova Irina V. Guzhova Boris A. Margulis 《Cell stress & chaperones》2013,18(3):391-396
The recent advances in designing Hsp70-based anti-cancer vaccines and the ability of the chaperone to penetrate inside a living cell prompted us to develop a non-invasive method for the treatment of surface tumors. We designed hydrogel-containing gel-forming substances and human recombinant Hsp70 and applied them on the surface of a 7-day-old B16F10 melanoma tumor. According to the results of histochemistry, Hsp70 diffused through skin layer inside the B16 tumor, and this transport was proved by biochemical data. The application of Hsp70 gel reduced the rate of tumor growth by 64 % and prolonged the life of animals by 46 %. Increased survival was correlated with the enhancement of B16-specific cytotoxicity and up-regulation of gamma–interferon production. Taken together, the data confirm the anti-tumor effect of pure recombinant Hsp70 delivered intratumorally and demonstrate the relevance of a novel non-invasive technology of Hsp70-based therapy. 相似文献
915.
Irina N. Shalova Katerina Cechalova Zuzana Rehakova Petya Dimitrova Elisa Ognibene Antonio Caprioli Elena V. Schmalhausen Vladimir I. Muronetz Luciano Saso 《Biochimica et Biophysica Acta (BBA)/General Subjects》2007
Recently, a relationship between glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the β-amyloid precursor protein (βAPP) in relationship with the pathogenesis of Alzheimer's disease (AD) has been suggested. Therefore, we studied the specific activity of GAPDH in the different animal models of AD: transgenic mice (Tg2576) and rats treated with β-amyloid, or thiorphan, or lipopolysaccharides (LPS) and interferon γ (INFγ). We observed that GAPDH activity was significantly decreased in the brain samples from TG mice. The injection of β-amyloid, or thiorphan, an inhibitor of neprilysin involved in β-amyloid catabolism, in rat brains resulted in a pronounced reduction of the enzyme activity. The infusion of LPS and IFNγ, which can influence the progression of the AD, significantly reduced the enzyme activity. 相似文献
916.
917.