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11.
Background
Although protein-protein interaction networks determined with high-throughput methods are incomplete, they are commonly used to infer the topology of the complete interactome. These partial networks often show a scale-free behavior with only a few proteins having many and the majority having only a few connections. Recently, the possibility was suggested that this scale-free nature may not actually reflect the topology of the complete interactome but could also be due to the error proneness and incompleteness of large-scale experiments. 相似文献12.
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14.
Pamonsinlapatham P Hadj-Slimane R Raynaud F Bickle M Corneloup C Barthelaix A Lepelletier Y Mercier P Schapira M Samson J Mathieu AL Hugo N Moncorgé O Mikaelian I Dufour S Garbay C Colas P 《PloS one》2008,3(8):e2902
The Ras GTPase-activating protein RasGAP catalyzes the conversion of active GTP-bound Ras into inactive GDP-bound Ras. However, RasGAP also acts as a positive effector of Ras and exerts an anti-apoptotic activity that is independent of its GAP function and that involves its SH3 (Src homology) domain. We used a combinatorial peptide aptamer approach to select a collection of RasGAP SH3 specific ligands. We mapped the peptide aptamer binding sites by performing yeast two-hybrid mating assays against a panel of RasGAP SH3 mutants. We examined the biological activity of a peptide aptamer targeting a pocket delineated by residues D295/7, L313 and W317. This aptamer shows a caspase-independent cytotoxic activity on tumor cell lines. It disrupts the interaction between RasGAP and Aurora B kinase. This work identifies the above-mentioned pocket as an interesting therapeutic target to pursue and points its cognate peptide aptamer as a promising guide to discover RasGAP small-molecule drug candidates. 相似文献
15.
Ajay Kumar Mishra Perrine Hugon Jean-Christophe Lagier Thi-Tien Nguyen Carine Couderc Didier Raoult Pierre-Edouard Fournier 《Standards in genomic sciences》2013,8(2):290-305
Enorma massiliensis strain phIT is the type strain of E. massiliensis gen. nov., sp. nov., the type species of a new genus within the family Coriobacteriaceae, Enorma gen. nov. This strain, whose genome is described here, was isolated from the fecal flora of a 26-year-old woman suffering from morbid obesity. E. massiliensis strain phIT is a Gram-positive, obligately anaerobic bacillus. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 2,280,571 bp long genome (1 chromosome but no plasmid) exhibits a G+C content of 62.0% and contains 1,901 protein-coding and 51 RNA genes, including 3 rRNA genes. 相似文献
16.
Karolina Kowalska Chantal Soscia Heather Combe Perrine Vasseur Romé Voulhoux Alain Filloux 《Biochimie》2010
Pseudomonas aeruginosa is an opportunistic pathogen, which causes numerous infections and can adopt a versatile lifestyle. During chronic infection, P. aeruginosa becomes established as a bacterial community known as a biofilm. Biofilm formation results from the production of a matrix mainly comprised of exopolysaccharides. P. aeruginosa possesses several gene clusters which contribute to the formation of the matrix, including the pel genes. Among the pel genes, pelC encodes an outer membrane protein, which may serve as a transporter of polysaccharide to the bacterial cell surface. Whereas outer membrane proteins usually display an amphipathic β-barrel fold, we show that PelC requires a C-terminal amphipathic α-helix for outer membrane insertion and function. Such a structural feature has only previously been reported for the Wza outer membrane protein of Escherichia coli, and our data suggest that this characteristic may be found in a large family of proteins, particularly outer membrane proteins specialized in polysaccharide transport. 相似文献
17.
Sarah E. Ross Alan R. Mardinly Alejandra E. McCord Jonathan Zurawski Sonia Cohen Cynthia Jung Linda Hu Stephanie I. Mok Anar Shah Erin M. Savner Christos Tolias Roman Corfas Suzhen Chen Perrine Inquimbert Yi Xu Roderick R. McInnes Frank L. Rice Gabriel Corfas Qiufu Ma Clifford J. Woolf Michael E. Greenberg 《Neuron》2010,65(6):886-898
18.
Acoustic signals transmit information by temporal characteristics and envelope periodicity as well as by their frequency content.
Many animals can extract the frequency content of a signal by means of specialized organs such as the cochlea but for the
detection and identification of higher-order periodicity, e.g., amplitude modulations, this type of organ is useless. In addition,
many animals do not have a cochlea but still depend on a reliable identification of different frequencies in the vast variety
of acoustic signals they perceive in their natural environment. Hence, neural mechanisms to decode periodicity information
must exist. We present a detailed mathematical analysis of a recurrent and a feedforward model of neuronal periodicity extraction
and discuss basic constraints for neuronal circuitry performing such a task in a biological system. Both the recurrent and
the feedforward model perform well using neuronal parameters typical for the auditory system. Performance is limited mainly
by the temporal precision of the connections between the neurons. 相似文献
19.
Brown CK Friedel HD Barker AR Buhse LF Keitel S Cecil TL Kraemer J Morris JM Reppas C Stickelmeyer MP Yomota C Shah VP 《AAPS PharmSciTech》2011,12(2):782-794
In 2003, the FIP Dissolution Working group published a position paper on dissolution/drug release testing for special/novel dosage forms that represented the scientific opinions of many experts in the field at that time (1). The position paper has supported activities, programs, and decisions in the scientific, technical, and regulatory community. Due to the rapid evolution of new practices and techniques for in vitro testing, the FIP Special Interest Group (SIG) on Dissolution/Drug Release decided to revise the previous paper and added proposals for further harmonization of in vitro release testing practices for different pharmaceutical dosage forms. This article represents the current updates to the previously published paper. This revision has been aligned to coincide with the USP taxonomy including route of administration, intended site of drug release, and dosage form. The revised paper includes information from current literature, expert discussions, and presentations from recent workshops (2,3). The authors acknowledge and expect further updates to be made as additional progress is made in the relevant areas. Thus, comments and additional contributions are welcome and may be considered for the next revision of the position paper. 相似文献
20.
Disentangling the roles of approach, activation and valence in instrumental and pavlovian responding
Huys QJ Cools R Gölzer M Friedel E Heinz A Dolan RJ Dayan P 《PLoS computational biology》2011,7(4):e1002028
Hard-wired, Pavlovian, responses elicited by predictions of rewards and punishments exert significant benevolent and malevolent influences over instrumentally-appropriate actions. These influences come in two main groups, defined along anatomical, pharmacological, behavioural and functional lines. Investigations of the influences have so far concentrated on the groups as a whole; here we take the critical step of looking inside each group, using a detailed reinforcement learning model to distinguish effects to do with value, specific actions, and general activation or inhibition. We show a high degree of sophistication in Pavlovian influences, with appetitive Pavlovian stimuli specifically promoting approach and inhibiting withdrawal, and aversive Pavlovian stimuli promoting withdrawal and inhibiting approach. These influences account for differences in the instrumental performance of approach and withdrawal behaviours. Finally, although losses are as informative as gains, we find that subjects neglect losses in their instrumental learning. Our findings argue for a view of the Pavlovian system as a constraint or prior, facilitating learning by alleviating computational costs that come with increased flexibility. 相似文献