全文获取类型
收费全文 | 938篇 |
免费 | 77篇 |
出版年
2023年 | 3篇 |
2022年 | 1篇 |
2021年 | 8篇 |
2020年 | 4篇 |
2019年 | 4篇 |
2018年 | 16篇 |
2017年 | 14篇 |
2016年 | 19篇 |
2015年 | 29篇 |
2014年 | 55篇 |
2013年 | 53篇 |
2012年 | 87篇 |
2011年 | 88篇 |
2010年 | 61篇 |
2009年 | 50篇 |
2008年 | 73篇 |
2007年 | 61篇 |
2006年 | 51篇 |
2005年 | 89篇 |
2004年 | 60篇 |
2003年 | 56篇 |
2002年 | 59篇 |
2001年 | 6篇 |
2000年 | 3篇 |
1999年 | 13篇 |
1998年 | 6篇 |
1997年 | 5篇 |
1996年 | 6篇 |
1995年 | 5篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1988年 | 4篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1978年 | 3篇 |
1977年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有1015条查询结果,搜索用时 15 毫秒
971.
Manal Sarkis Maria A. Miteva Maria Chiara Dasso Lang Maryse Jaouen Marie‐Agnès Sari Marie‐Odile Galcéra Mélanie Ethève‐Quelquejeu Christiane Garbay Gildas Bertho Emmanuelle Braud 《Proteins》2017,85(4):593-601
CDC25 phosphatases play a crucial role in cell cycle regulation. They have been found to be over‐expressed in various human tumours and to be valuable targets for cancer treatment. Here, we report the first model of binding of the most potent CDC25 inhibitor to date, the bis‐quinone IRC‐083864, into CDC25B obtained by combining molecular modeling and NMR studies. Our study provides new insights into key interactions of the catalytic site inhibitor and CDC25B in the absence of any available experimental structure of CDC25 with a bound catalytic site inhibitor. The docking model reveals that IRC‐083864 occupies both the active site and the inhibitor binding pocket of the CDC25B catalytic domain. NMR saturation transfer difference and WaterLOGSY data indicate the binding zones of the inhibitor and support the docking model. Probing interactions of analogues of the two quinone units of IRC‐083864 with CDC25B demonstrate that IRC‐083864 competes with each monomer. Proteins 2017; 85:593–601. © 2016 Wiley Periodicals, Inc. 相似文献
972.
Marie Messmer Agnès Gaudry Marie Sissler Catherine Florentz 《RNA (New York, N.Y.)》2009,15(8):1462-1468
More than 130 mutations in human mitochondrial tRNA (mt-tRNA) genes have been correlated with a variety of neurodegenerative and neuromuscular disorders. Their molecular impacts are of mosaic type, affecting various stages of tRNA biogenesis, structure, and/or functions in mt-translation. Knowledge of mammalian mt-tRNA structures per se remains scarce however. Primary and secondary structures deviate from classical tRNAs, while rules for three-dimensional (3D) folding are almost unknown. Here, we take advantage of a myopathy-related mutation A7526G (A9G) in mt-tRNAAsp to investigate both the primary molecular impact underlying the pathology and the role of nucleotide 9 in the network of 3D tertiary interactions. Experimental evidence is presented for existence of a 9-12-23 triple in human mt-tRNAAsp with a strongly conserved interaction scheme in mammalian mt-tRNAs. Mutation A7526G disrupts the triple interaction and in turn reduces aspartylation efficiency. 相似文献
973.
Bernard J Harb C Mortier E Quéméner A Meloen RH Vermot-Desroches C Wijdeness J van Dijken P Grötzinger J Slootstra JW Plet A Jacques Y 《The Journal of biological chemistry》2004,279(23):24313-24322
To identify the epitopes in human interleukin-15 (IL-15) that are responsible for binding to the interleukin-15 receptor alpha chain, antibody and receptor mapping by peptide scanning and site-directed mutagenesis was used. By using peptide scanning, we identified four regions in IL-15. The first region ((85)CKECEELEEKN(95)) is located in the C-D loop and is recognized by a set of non-inhibitory antibodies. The second region ((102)SFVHIVQMFIN(112)) is located in helix D and is recognized by two antibodies that are inhibitory of IL-15 bio-activity but not of IL-15 binding to IL-15Ralpha. The two remaining regions react with a recombinant soluble form of the IL-15Ralpha; the first ((44)LLELQVISL(52), peptide 1) corresponds to a sequence located in the B-helix and the second ((64)ENLII(68), peptide 2) to a sequence located in helix C. The latter is also contained in the epitope recognized by an antibody (monoclonal antibody B-E29) that prevents IL-15 binding to IL-15Ralpha. By site-directed mutagenesis, we confirmed that residues present in peptide 1 (Leu-45, Glu-46, Val-49, Ser-51, and Leu-52) and peptide 2 (Leu-66 and Ile-67) are involved in the binding of IL-15 to IL-15Ralpha. Furthermore, the results presented indicate that residues in the second peptide (Glu-64, Asn-65, and Ile-68) participate in IL-2Rbeta recruitment. This finding could have implications for the dynamics of receptor assembly. These results also indicate that the modes of interaction of IL-15 and IL-2 with their respective alpha chains are not completely analogous. Finally, some of the IL-15 mutants generated in this study displayed agonist or antagonist properties and may be useful as therapeutic agents. 相似文献
974.
975.
The genus Abatus (Echinoidea: Spatangoida: Schizasteridae), endemic to the Southern Ocean, consists of several species which, like many other Antarctic marine invertebrates, brood their offspring. The modality of fertilization is not known in these species, whose direct observation and sampling are difficult. Parentage analyses by means of molecular markers may help to gain information on this stage of the life-cycle. In this pilot study, we analysed a brooding female and her offspring with dominant molecular markers—RAPD (Random Amplified Polymorphic DNA). We established that each cohort present in the brooding pouches, i.e. gastrulae and juveniles, originated from at least two distinct father genotypes. Our original method of analysis of dominant marker data should have vast applications since it allows one to test, not only (1) the hypothesis that the progeny of a given mother originates from a single father, but also (2) the temporal stability of the paternal gene pool. 相似文献
976.
Catherine Bonaïti-Pellié Agnès Chompret Marie-France Tournade Jean Lemerle Paul A. Voute Jan F. M. Delemarre 《Human genetics》1993,91(4):373-376
Referring to the mutational theory of carcinogenesis in embryonal tumors, it is commonly accepted that patients with multifocal tumors are hereditary cases. This is based on the implicit assumption that each tumor results from a single mutational event occurring in a cell that has already inherited a mutation, and that these tumors are independent. We studied the distribution of tumors in 1,868 cases where the focality was known (SIOP 1, 2, 5 and 6). Using all the supposed gene carriers (bilateral and unilateral multifocal cases), and assuming a Poisson distribution of tumors, we estimated the mean number m of tumors in each kidney to be 0.37. Comparing the observed distribution of cases to the expected one, we found a very bad fit to this hypothesis (P<10-9). This is due to an excess of multifocal tumors, particularly in unilateral cases. These findings have important implications in genetic counseling, since the usual practice of considering multifocal tumor patients as hereditary cases may result in a large overestimate of the recurrence risk in such cases. The implications for the mechanisms of tumor development are also discussed. 相似文献
977.
978.
The influence of the annual spring floods on small mammal communities was studied in the Nemunas River Delta, SW Lithuania. The aim of the investigation was to compare the diversity of small mammals inhabiting spring-flooded meadows, meadows not subjected to flooding and spring-flooded forest in years characterized by differing heights and durations of spring flood. In the years of the high flood, the number of species and diversity index were higher, while index of dominance was less than in the years of low flood. Significantly, the highest proportions of Apodemus agrarius were recorded in spring-flooded meadows in years of high flood (41.7%), while Microtus oeconomus occurred in the highest proportions in spring-flooded meadows in years of low flood (66.8%) and in meadows not subjected to flooding (47.1%). In non-flooded areas, M. Oeconomus is not expelled by the floods and outcompetes other species. After high levels of flooding, during the process of re-population, the voles may be outcompeted by A. agrarius. In the absence of dominant species, greater opportunities existed for the establishment of more species (13 species in flooded meadows). Micromys minutus accounted for up to 19.5–30.1% in the years of high flood. We concluded that the annual spring floods in the Nemunas Delta had no long-term negative effects, the number of small mammal species and their abundance had been restored in just a few months. The worst consequences of the high flood were recorded in forest habitat. Spring floods, and especially the higher floods, are natural environmental agents, maintaining the high diversity of small mammals in meadows and reed-beds. 相似文献
979.
Corinne Biderre-Petit Jean-Christophe Charvy Gisèle Bronner Marina Chauvet Didier Debroas Hélène Gardon Claire Hennequin Isabelle Jouan-Dufournel Anne Moné Arthur Monjot Viviane Ravet Agnès Vellet Cécile Lepère 《Molecular ecology resources》2023,23(1):222-232
Freshwater is a critical resource for human survival but severely threatened by anthropogenic activities and climate change. These changes strongly impact the abundance and diversity of the microbial communities which are key players in the functioning of these aquatic ecosystems. Although widely documented since the emergence of high-throughput sequencing approaches, the information on these natural microbial communities is scattered among thousands of publications and it is therefore difficult to investigate the temporal dynamics and the spatial distribution of microbial taxa within or across ecosystems. To fill this gap and in the FAIR principles context we built a manually curated and standardized microbial freshwater –omics database (FreshOmics). Based on recognized ontologies (ENVO, MIMICS, GO, ISO), FreshOmics describes 29 different types of freshwater ecosystems and uses standardized attributes to depict biological samples, sequencing protocols and article attributes for more than 2487 geographical locations across 71 countries around the world. The database contains 24,808 sequence identifiers (i.e., Run_Id / Exp_ID, mainly from SRA/DDBJ SRA/ENA, GSA and MG-RAST repositories) covering all sequence-based -omics approaches used to investigate bacteria, archaea, microbial eukaryotes, and viruses. Therefore, FreshOmics allows accurate and comprehensive analyses of microbial communities to answer questions related to their roles in freshwater ecosystems functioning and resilience, especially through meta-analysis studies. This collection also highlights different sort of errors in published works (e.g., wrong coordinates, sample type, material, spelling). 相似文献
980.
Path planning versus cue responding: a bio-inspired model of switching between navigation strategies
Laurent Dollé Denis Sheynikhovich Benoît Girard Ricardo Chavarriaga Agnès Guillot 《Biological cybernetics》2010,103(4):299-317
In this article, we describe a new computational model of switching between path-planning and cue-guided navigation strategies.
It is based on three main assumptions: (i) the strategies are mediated by separate memory systems that learn independently
and in parallel; (ii) the learning algorithms are different in the two memory systems—the cue-guided strategy uses a temporal-difference
(TD) learning rule to approach a visible goal, whereas the path-planning strategy relies on a place-cell-based graph-search
algorithm to learn the location of a hidden goal; (iii) a strategy selection mechanism uses TD-learning rule to choose the
most successful strategy based on past experience. We propose a novel criterion for strategy selection based on the directions
of goal-oriented movements suggested by the different strategies. We show that the selection criterion based on this “common
currency” is capable of choosing the best among TD-learning and planning strategies and can be used to solve navigational
tasks in continuous state and action spaces. The model has been successfully applied to reproduce rat behavior in two water-maze
tasks in which the two strategies were shown to interact. The model was used to analyze competitive and cooperative interactions
between different strategies during these tasks as well as relative influence of different types of sensory cues. 相似文献