全文获取类型
收费全文 | 1200篇 |
免费 | 78篇 |
专业分类
1278篇 |
出版年
2023年 | 14篇 |
2022年 | 27篇 |
2021年 | 34篇 |
2020年 | 20篇 |
2019年 | 29篇 |
2018年 | 35篇 |
2017年 | 30篇 |
2016年 | 40篇 |
2015年 | 58篇 |
2014年 | 59篇 |
2013年 | 106篇 |
2012年 | 100篇 |
2011年 | 87篇 |
2010年 | 54篇 |
2009年 | 59篇 |
2008年 | 77篇 |
2007年 | 45篇 |
2006年 | 59篇 |
2005年 | 53篇 |
2004年 | 43篇 |
2003年 | 53篇 |
2002年 | 45篇 |
2001年 | 16篇 |
2000年 | 5篇 |
1999年 | 12篇 |
1998年 | 11篇 |
1997年 | 6篇 |
1996年 | 10篇 |
1995年 | 7篇 |
1994年 | 7篇 |
1993年 | 9篇 |
1992年 | 3篇 |
1991年 | 5篇 |
1990年 | 4篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 6篇 |
1986年 | 4篇 |
1985年 | 3篇 |
1984年 | 7篇 |
1983年 | 2篇 |
1981年 | 2篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1968年 | 2篇 |
1967年 | 2篇 |
1966年 | 2篇 |
1933年 | 1篇 |
1915年 | 1篇 |
1911年 | 1篇 |
排序方式: 共有1278条查询结果,搜索用时 15 毫秒
121.
122.
Francesca Ghirga Federica Aiello Sara Toscano Cinzia Ingallina Mariangela Siler Danilo Cucchi Agnese Po Evelina Miele Davide D'Amico Gianluca Canettieri Enrico De Smaele Elisabetta Ferretti Isabella Screpanti Gloria Uccello Barretta Maurizio Botta Bruno Botta Alberto Gulino Lucia Di Marcotullio 《The EMBO journal》2015,34(2):200-217
123.
Konstantin Byrgazov Irina Grishkovskaya Stefan Arenz Nicolas Coudevylle Hannes Temmel Daniel N. Wilson Kristina Djinovic-Carugo Isabella Moll 《Nucleic acids research》2015,43(1):661-673
In Gram-negative bacteria, the multi-domain protein S1 is essential for translation initiation, as it recruits the mRNA and facilitates its localization in the decoding centre. In sharp contrast to its functional importance, S1 is still lacking from the high-resolution structures available for Escherichia coli and Thermus thermophilus ribosomes and thus the molecular mechanism governing the S1–ribosome interaction has still remained elusive. Here, we present the structure of the N-terminal S1 domain D1 when bound to the ribosome at atomic resolution by using a combination of NMR, X-ray crystallography and cryo-electron microscopy. Together with biochemical assays, the structure reveals that S1 is anchored to the ribosome primarily via a stabilizing π-stacking interaction within the short but conserved N-terminal segment that is flexibly connected to domain D1. This interaction is further stabilized by salt bridges involving the zinc binding pocket of protein S2. Overall, this work provides one hitherto enigmatic piece in the ′ribosome puzzle′, namely the detailed molecular insight into the topology of the S1–ribosome interface. Moreover, our data suggest novel mechanisms that have the potential to modulate protein synthesis in response to environmental cues by changing the affinity of S1 for the ribosome. 相似文献
124.
Qian Jiang Stacey Arnold Tiffany Heanue Krishna?Praneeth Kilambi Betty Doan Ashish Kapoor Albee?Yun Ling Maria?X. Sosa Moltu Guy Qingguang Jiang Grzegorz Burzynski Kristen West Seneca Bessling Paola Griseri Jeanne Amiel Raquel?M. Fernandez Joke?B.G.M. Verheij Robert?M.W. Hofstra Salud Borrego Stanislas Lyonnet Isabella Ceccherini Jeffrey?J. Gray Vassilis Pachnis Andrew?S. McCallion Aravinda Chakravarti 《American journal of human genetics》2015,96(4):581-596
Innervation of the gut is segmentally lost in Hirschsprung disease (HSCR), a consequence of cell-autonomous and non-autonomous defects in enteric neuronal cell differentiation, proliferation, migration, or survival. Rare, high-penetrance coding variants and common, low-penetrance non-coding variants in 13 genes are known to underlie HSCR risk, with the most frequent variants in the ret proto-oncogene (RET). We used a genome-wide association (220 trios) and replication (429 trios) study to reveal a second non-coding variant distal to RET and a non-coding allele on chromosome 7 within the class 3 Semaphorin gene cluster. Analysis in Ret wild-type and Ret-null mice demonstrates specific expression of Sema3a, Sema3c, and Sema3d in the enteric nervous system (ENS). In zebrafish embryos, sema3 knockdowns show reduction of migratory ENS precursors with complete ablation under conjoint ret loss of function. Seven candidate receptors of Sema3 proteins are also expressed within the mouse ENS and their expression is also lost in the ENS of Ret-null embryos. Sequencing of SEMA3A, SEMA3C, and SEMA3D in 254 HSCR-affected subjects followed by in silico protein structure modeling and functional analyses identified five disease-associated alleles with loss-of-function defects in semaphorin dimerization and binding to their cognate neuropilin and plexin receptors. Thus, semaphorin 3C/3D signaling is an evolutionarily conserved regulator of ENS development whose dys-regulation is a cause of enteric aganglionosis. 相似文献
125.
Detection of Phosphorylated Insulin Receptor in Colorectal Adenoma and Adenocarcinoma: Implications for Prognosis and Clinical Outcome 下载免费PDF全文
126.
Enhanced Expression of Indoleamine 2,3‐Dioxygenase in Helicobacter pylori‐Infected Human Gastric Mucosa Modulates Th1/Th2 Pathway and Interleukin 17 Production 下载免费PDF全文
127.
Protecting osmolytes are widespread small organic molecules able to stabilize the folded state of most proteins against various denaturing stresses in vivo. The osmophobic model explains thermodynamically their action through a preferential exclusion of the osmolyte molecules from the protein surface, thus favoring the formation of intrapeptide hydrogen bonds. Few works addressed the influence of protecting osmolytes on the protein unfolding transition state and kinetics. Among those, previous single molecule force spectroscopy experiments evidenced a complexation of the protecting osmolyte molecules at the unfolding transition state of the protein, in apparent contradiction with the osmophobic nature of the protein backbone. We present single-molecule evidence that glycerol, which is a ubiquitous protecting osmolyte, stabilizes a globular protein against mechanical unfolding without binding into its unfolding transition state structure. We show experimentally that glycerol does not change the position of the unfolding transition state as projected onto the mechanical reaction coordinate. Moreover, we compute theoretically the projection of the unfolding transition state onto two other common reaction coordinates, that is, the number of native peptide bonds and the weighted number of native contacts. To that end, we augment an analytic Ising-like protein model with support for group-transfer free energies. Using this model, we find again that the position of the unfolding transition state does not change in the presence of glycerol, giving further support to the conclusions based on the single-molecule experiments. 相似文献
128.
Gemma S Butini S Campiani G Brindisi M Zanoli S Romano MP Tripaldi P Savini L Fiorini I Borrelli G Novellino E Maga G 《Bioorganic & medicinal chemistry letters》2011,21(9):2776-2779
Among the enzymes involved in the life cycle of HCV, the non-structural protein NS3, with its double function of protease and NTPase/helicase, is essential for the virus replication. Exploiting our previous knowledge in the development of nucleotide-mimicking NS3 helicase (NS3h) inhibitors endowed with key structural and electronic features necessary for an optimal ligand-enzyme interaction, we developed the tetrahydroacridinyl derivative 3a as the most potent NS3h competitive inhibitor reported to date (HCV NS3h K(i)=20 nM). 相似文献
129.
Bartolini B Chillemi G Abbate I Bruselles A Rozera G Castrignanò T Paoletti D Picardi E Desideri A Pesole G Capobianchi MR 《The new microbiologica》2011,34(4):391-397
De novo high-throughput pyrosequencing was used to detect and characterize 2009 pandemic influenza A (H1N1) virus directly in nasopharyngeal swabs in the context of the microbial community. Data were generated with a prior sequence independent amplification by 454 pyrosequencing on GS-FLX platform (Roche). Influenza A assembled reads allowed near full-length genome reconstruction with the simultaneous analysis of site-specific heterogeneity. The molecular approach applied proved to be a powerful tool to characterize the new pandemic H1N1 influenza virus in clinical samples. This approach could be of great value in identifying possibly new reassortants that may occur in the near future. 相似文献
130.
Support systems play an important role for the communication between users and developers of software. We studied two support systems, an issues tracker and an email service available for Scratchpads, a Web 2.0 social networking tool that enables communities to build, share, manage and publish biodiversity information on the Web. Our aim was to identify co-learning opportunities between users and developers of the Scratchpad system by asking which support system was used by whom and for what type of questions. Our results show that issues tracker and emails cater to different user mentalities as well as different kind of questions and suggest ways to improve the support system as part of the development under the EU funded ViBRANT programme. 相似文献