全文获取类型
收费全文 | 102篇 |
免费 | 42篇 |
出版年
2021年 | 2篇 |
2020年 | 3篇 |
2019年 | 2篇 |
2018年 | 4篇 |
2017年 | 1篇 |
2016年 | 2篇 |
2015年 | 9篇 |
2014年 | 13篇 |
2013年 | 7篇 |
2012年 | 9篇 |
2011年 | 9篇 |
2010年 | 6篇 |
2009年 | 4篇 |
2008年 | 9篇 |
2007年 | 6篇 |
2006年 | 6篇 |
2005年 | 6篇 |
2004年 | 6篇 |
2003年 | 6篇 |
2002年 | 3篇 |
2001年 | 3篇 |
2000年 | 8篇 |
1999年 | 5篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1981年 | 1篇 |
1977年 | 2篇 |
1970年 | 2篇 |
排序方式: 共有144条查询结果,搜索用时 0 毫秒
141.
Roelie L. KingmaHarm J. Snijder Bauke W. DijkstraNiek Dekker Maarten R. Egmond 《生物化学与生物物理学报:生物膜》2002,1561(2):230-237
Outer membrane phospholipase A (OMPLA) is an integral membrane enzyme that hydrolyses phospholipids requiring Ca2+ as cofactor. In vitro studies have shown that OMPLA is only active as a dimer. The structures of monomeric and dimeric OMPLA provided possible clues to the activation process. In the inhibited dimeric species calcium ions are located at the dimer interface ideally suited to stabilise the oxyanion intermediates formed during catalysis. The side chain hydroxyl function of Ser152 is one of the ligands of this interfacial calcium. In the crystal structure of monomeric OMPLA the interfacial calcium site is lacking, but calcium was found to bind at a site involving the carboxylates of Asp149 and Asp184. In the current study the relevance of the identified calcium sites has been studied by site-directed mutagenesis. The Ser152Asn variant confirmed the importance of the interfacial calcium site for catalysis, and also demonstrated that this site is essentially involved in the dimerisation process. Replacements of the ligands in monomeric OMPLA, i.e. Asp149Asn, Asp149Ala and Asp184Asn, only showed minor effects on catalytic activity and dimerisation. A stronger effect observed for the variant Asp184Ala was explained by the proximity of Asp184 to the catalytically important Ser152 residue. We propose that Asp149 and Asp184 provide an electronegative funnel that may facilitate Ca2+ transfer to the interfacial calcium site. 相似文献
142.
J A Snijder 《BMJ (Clinical research ed.)》1977,1(6065):905-906
143.
Chris Lauber Jelle J. Goeman Maria del Carmen Parquet Phan Thi Nga Eric J. Snijder Kouichi Morita Alexander E. Gorbalenya 《PLoS pathogens》2013,9(7)
The small size of RNA virus genomes (2-to-32 kb) has been attributed to high mutation rates during replication, which is thought to lack proof-reading. This paradigm is being revisited owing to the discovery of a 3′-to-5′ exoribonuclease (ExoN) in nidoviruses, a monophyletic group of positive-stranded RNA viruses with a conserved genome architecture. ExoN, a homolog of canonical DNA proof-reading enzymes, is exclusively encoded by nidoviruses with genomes larger than 20 kb. All other known non-segmented RNA viruses have smaller genomes. Here we use evolutionary analyses to show that the two- to three-fold expansion of the nidovirus genome was accompanied by a large number of replacements in conserved proteins at a scale comparable to that in the Tree of Life. To unravel common evolutionary patterns in such genetically diverse viruses, we established the relation between genomic regions in nidoviruses in a sequence alignment-free manner. We exploited the conservation of the genome architecture to partition each genome into five non-overlapping regions: 5′ untranslated region (UTR), open reading frame (ORF) 1a, ORF1b, 3′ORFs (encompassing the 3′-proximal ORFs), and 3′ UTR. Each region was analyzed for its contribution to genome size change under different models. The non-linear model statistically outperformed the linear one and captured >92% of data variation. Accordingly, nidovirus genomes were concluded to have reached different points on an expansion trajectory dominated by consecutive increases of ORF1b, ORF1a, and 3′ORFs. Our findings indicate a unidirectional hierarchical relation between these genome regions, which are distinguished by their expression mechanism. In contrast, these regions cooperate bi-directionally on a functional level in the virus life cycle, in which they predominantly control genome replication, genome expression, and virus dissemination, respectively. Collectively, our findings suggest that genome architecture and the associated region-specific division of labor leave a footprint on genome expansion and may limit RNA genome size. 相似文献
144.