全文获取类型
收费全文 | 1222篇 |
免费 | 126篇 |
专业分类
1348篇 |
出版年
2024年 | 1篇 |
2023年 | 11篇 |
2022年 | 24篇 |
2021年 | 31篇 |
2020年 | 25篇 |
2019年 | 27篇 |
2018年 | 24篇 |
2017年 | 41篇 |
2016年 | 48篇 |
2015年 | 81篇 |
2014年 | 86篇 |
2013年 | 90篇 |
2012年 | 124篇 |
2011年 | 101篇 |
2010年 | 71篇 |
2009年 | 78篇 |
2008年 | 85篇 |
2007年 | 98篇 |
2006年 | 62篇 |
2005年 | 56篇 |
2004年 | 57篇 |
2003年 | 33篇 |
2002年 | 47篇 |
2001年 | 7篇 |
2000年 | 2篇 |
1999年 | 4篇 |
1998年 | 7篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1990年 | 1篇 |
1988年 | 2篇 |
1984年 | 1篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有1348条查询结果,搜索用时 15 毫秒
231.
232.
Caroline Lacroux Stéphanie Simon Sylvie L. Benestad Séverine Maillet Jacinthe Mathey Séverine Lugan Fabien Corbière Hervé Cassard Pierrette Costes Dominique Bergonier Jean-Louis Weisbecker Torffin Moldal Hugh Simmons Frederic Lantier Cécile Feraudet-Tarisse Nathalie Morel Fran?ois Schelcher Jacques Grassi Olivier Andréoletti 《PLoS pathogens》2008,4(12)
Since prion infectivity had never been reported in milk, dairy products originating from transmissible spongiform encephalopathy (TSE)-affected ruminant flocks currently enter unrestricted into the animal and human food chain. However, a recently published study brought the first evidence of the presence of prions in mammary secretions from scrapie-affected ewes. Here we report the detection of consistent levels of infectivity in colostrum and milk from sheep incubating natural scrapie, several months prior to clinical onset. Additionally, abnormal PrP was detected, by immunohistochemistry and PET blot, in lacteal ducts and mammary acini. This PrPSc accumulation was detected only in ewes harbouring mammary ectopic lymphoid follicles that developed consequent to Maedi lentivirus infection. However, bioassay revealed that prion infectivity was present in milk and colostrum, not only from ewes with such lympho-proliferative chronic mastitis, but also from those displaying lesion-free mammary glands. In milk and colostrum, infectivity could be recovered in the cellular, cream, and casein-whey fractions. In our samples, using a Tg 338 mouse model, the highest per ml infectious titre measured was found to be equivalent to that contained in 6 µg of a posterior brain stem from a terminally scrapie-affected ewe. These findings indicate that both colostrum and milk from small ruminants incubating TSE could contribute to the animal TSE transmission process, either directly or through the presence of milk-derived material in animal feedstuffs. It also raises some concern with regard to the risk to humans of TSE exposure associated with milk products from ovine and other TSE-susceptible dairy species. 相似文献
233.
Mercier R Jolivet S Vignard J Durand S Drouaud J Pelletier G Nogué F 《Genetics》2008,180(4):2295-2297
The reappearance of HTH alleles in the offspring of homozygous Arabidopsis hth mutants is not consistent with classical Mendelian genetics. It has been suggested that stored RNA may be used to restore genetic information. However, Peng et al. reported that hth mutants tend to display outcrossing and suggested that outcrossing might provide an alternative explanation for the apparent genetic instability. We have confirmed and extended these results, corroborating that the apparent non-Mendelian behavior of hth mutants can be explained by their susceptibility to outcrossing. 相似文献
234.
235.
Fabien Corblin Sbastien Tripodi Eric Fanchon Delphine Ropers Laurent Trilling 《Bio Systems》2009,98(2):91-104
Dynamical modeling has proven useful for understanding how complex biological processes emerge from the many components and interactions composing genetic regulatory networks (GRNs). However, the development of models is hampered by large uncertainties in both the network structure and parameter values. To remedy this problem, the models are usually developed through an iterative process based on numerous simulations, confronting model predictions with experimental data and refining the model structure and/or parameter values to repair the inconsistencies. In this paper, we propose an alternative to this generate-and-test approach. We present a four-step method for the systematic construction and analysis of discrete models of GRNs by means of a declarative approach. Instead of instantiating the models as in classical modeling approaches, the biological knowledge on the network structure and its dynamics is formulated in the form of constraints. The compatibility of the network structure with the constraints is queried and in case of inconsistencies, some constraints are relaxed. Common properties of the consistent models are then analyzed by means of dedicated languages. Two such languages are introduced in the paper. Removing questionable constraints or adding interesting ones allows to further analyze the models. This approach allows to identify the best experiments to be carried out, in order to discriminate sets of consistent models and refine our knowledge on the system functioning. We test the feasibility of our approach, by applying it to the re-examination of a model describing the nutritional stress response in the bacterium Escherichia coli. 相似文献
236.
Francis Repoila Fabien Darfeuille 《Biology of the cell / under the auspices of the European Cell Biology Organization》2009,101(2):117-131
Regulatory ncRNAs (non‐coding RNAs) adjust bacterial physiology in response to environmental cues. ncRNAs can base‐pair to mRNAs and change their translation efficiency and/or their stability, or they can bind to proteins and modulate their activity. ncRNAs have been discovered in several species throughout the bacterial kingdom. This review illustrates the diversity of physiological processes and molecular mechanisms where ncRNAs are key regulators. 相似文献
237.
Fabien Marpeau Aditya Barua Krešimir Josić 《Journal of computational neuroscience》2009,26(3):445-457
The stochastic integrate and fire neuron is one of the most commonly used stochastic models in neuroscience. Although some
cases are analytically tractable, a full analysis typically calls for numerical simulations. We present a fast and accurate
finite volume method to approximate the solution of the associated Fokker-Planck equation. The discretization of the boundary
conditions offers a particular challenge, as standard operator splitting approaches cannot be applied without modification.
We demonstrate the method using stationary and time dependent inputs, and compare them with Monte Carlo simulations. Such
simulations are relatively easy to implement, but can suffer from convergence difficulties and long run times. In comparison,
our method offers improved accuracy, and decreases computation times by several orders of magnitude. The method can easily
be extended to two and three dimensional Fokker-Planck equations.
相似文献
Fabien MarpeauEmail: |
238.
Fabien Vincent Margaret T. Nguyen Daniel E. Emerling Michael G. Kelly Matthew A.J. Duncton 《Bioorganic & medicinal chemistry letters》2009,19(23):6793-6796
The screening of known medicinal agents against new biological targets has been shown to be a valuable approach for revealing new pharmacology of marketed compounds. Recently, carbamate, urea and ketone inhibitors of fatty acid amide hydrolase (FAAH) have been described as promising treatments for pain, anxiety, depression and other CNS-related conditions. In order to find novel FAAH inhibitors, a focused screen of molecules containing potentially reactive moieties or having in vivo effects that are possibly relevant to the biology of FAAH was conducted. These studies revealed phenmedipham 13 and amperozide 14 to be inhibitors of human FAAH, with an IC50 of 377 nM and 1.34 μM, respectively. 相似文献
239.
John Porter Simon Lumb Richard J. Franklin Jose M. Gascon-Simorte Mark Calmiano Kelly Le Riche Bénédicte Lallemand Jean Keyaerts Helen Edwards Alison Maloney Jean Delgado Lloyd King Anne Foley Fabien Lecomte James Reuberson Christoph Meier Mark Batchelor 《Bioorganic & medicinal chemistry letters》2009,19(10):2780-2784
A series of 4-azaindole inhibitors of c-Met kinase is described. The postulated binding mode was confirmed by an X-ray crystal structure and series optimisation was performed on the basis of this structure. Future directions for series development are discussed. 相似文献
240.