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21.
Mark S. Tichenor John M. Keith William M. Jones Joan M. Pierce Jeff Merit Natalie Hawryluk Mark Seierstad James A. Palmer Michael Webb Mark J. Karbarz Sandy J. Wilson Michelle L. Wennerholm Filip Woestenborghs Dominiek Beerens Lin Luo Sean M. Brown Marlies De Boeck Sandra R. Chaplan J. Guy Breitenbucher 《Bioorganic & medicinal chemistry letters》2012,22(24):7357-7362
The structure–activity relationships for a series of heteroaryl urea inhibitors of fatty acid amide hydrolase (FAAH) are described. Members of this class of inhibitors have been shown to inactivate FAAH by covalent modification of an active site serine with subsequent release of an aromatic amine from the urea electrophile. Systematic Ames II testing guided the optimization of urea substituents by defining the structure–mutagenicity relationships for the released aromatic amine metabolites. Potent FAAH inhibitors were identified having heteroaryl amine leaving groups that were non-mutagenic in the Ames II assay. 相似文献
22.
Vasey N 《American journal of primatology》2005,66(1):1-6
The papers in this issue were presented at a symposium during the 25th Annual Meeting of the American Society of Primatologists held in Oklahoma City, Oklahoma, in June 2002. This symposium brought together many of the scientists who have contributed to our knowledge of ruffed lemur ecology, behavior, and conservation in the past decade. One objective was to share and compare key findings about ruffed lemurs (Varecia) resulting from long-term field studies at various sites in Madagascar. A second objective was to cross-fertilize work being done in the wild with that being done in captivity, with the aim of advancing a common conservation mission for this critically endangered genus. Varecia is a prime candidate for synthetic assessments such as these because it has now been studied in both the northern and southern reaches of its geographic range, and has also been the focus of a captive-to-wild reinforcement project. The papers in this issue contribute to 1) the establishment of reference ranges for a suite of physiological parameters in healthy wild Varecia populations; 2) environmental enrichment aimed at preserving species-typical behaviors in captivity; 3) an understanding of how forest structure, floristic composition, and fruiting phenology in areas with differing disturbance histories correlate with the natural occurrence and abundance of Varecia; 4) primary knowledge concerning dominance relations between the sexes and group leadership in wild Varecia; and 5) primary knowledge concerning how wild Varecia, with their unusual reproductive pattern and heavy reliance on fruit, modulate their activity budgets seasonally and in tandem with reproductive stages. 相似文献
23.
Florian Wilfling Huajin Wang Joel T. Haas Natalie Krahmer Travis J. Gould Aki Uchida Ji-Xin Cheng Morven Graham Romain Christiano Florian Fröhlich Xinran Liu Kimberly K. Buhman Rosalind A. Coleman Joerg Bewersdorf Robert V. Farese Tobias C. Walther 《Developmental cell》2013,24(4):384-399
Highlights? Triacylglyceride (TG) synthesis is coupled with lipid droplet (LD) growth ? Two LD populations exist: growing LDs, containing TG enzymes, and small LDs ? Specific TG synthesis enzymes move from the ER to LDs through membrane bridges ? LD localization of TG enzymes mediates expansion of a subset of LDs 相似文献
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Mucin glycoproteins with large numbers of O-linked glycosylations comprise the mucosal barrier lining the mammalian gastrointestinal tract from mouth to gut. A critical biological function of mucins is to protect the underlying epithelium from infection. Enterohemorrhagic Escherichia coli (EHEC), the mediator of severe food- and water-borne disease, can breach this barrier and adhere to intestinal cells. StcE, a ~100 kDa metalloprotease secreted by EHEC, plays a pivotal role in remodeling the mucosal lining during infection. To obtain mechanistic insight into its function, we have determined the structure of StcE. Our data reveal a dynamic, multidomain architecture featuring an unusually large substrate-binding cleft and a prominent polarized surface charge distribution highly suggestive of an electrostatic role in substrate targeting. The observation of key conserved motifs in the active site allows us to propose the structural basis for the specific recognition of α-O-glycan-containing substrates. Complementary biochemical analysis provides further insight into its distinct substrate specificity and binding stoichiometry. 相似文献
26.
Yedael Y. Waldman Arjun Biddanda Natalie R. Davidson Paul Billing-Ross Maya Dubrovsky Christopher L. Campbell Carole Oddoux Eitan Friedman Gil Atzmon Eran Halperin Harry Ostrer Alon Keinan 《PloS one》2016,11(3)
The Bene Israel Jewish community from West India is a unique population whose history before the 18th century remains largely unknown. Bene Israel members consider themselves as descendants of Jews, yet the identity of Jewish ancestors and their arrival time to India are unknown, with speculations on arrival time varying between the 8th century BCE and the 6th century CE. Here, we characterize the genetic history of Bene Israel by collecting and genotyping 18 Bene Israel individuals. Combining with 486 individuals from 41 other Jewish, Indian and Pakistani populations, and additional individuals from worldwide populations, we conducted comprehensive genome-wide analyses based on FST, principal component analysis, ADMIXTURE, identity-by-descent sharing, admixture linkage disequilibrium decay, haplotype sharing and allele sharing autocorrelation decay, as well as contrasted patterns between the X chromosome and the autosomes. The genetics of Bene Israel individuals resemble local Indian populations, while at the same time constituting a clearly separated and unique population in India. They are unique among Indian and Pakistani populations we analyzed in sharing considerable genetic ancestry with other Jewish populations. Putting together the results from all analyses point to Bene Israel being an admixed population with both Jewish and Indian ancestry, with the genetic contribution of each of these ancestral populations being substantial. The admixture took place in the last millennium, about 19–33 generations ago. It involved Middle-Eastern Jews and was sex-biased, with more male Jewish and local female contribution. It was followed by a population bottleneck and high endogamy, which can lead to increased prevalence of recessive diseases in this population. This study provides an example of how genetic analysis advances our knowledge of human history in cases where other disciplines lack the relevant data to do so. 相似文献
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28.
Víctor Faundes William G. Newman Laura Bernardini Natalie Canham Jill Clayton-Smith Bruno Dallapiccola Sally J. Davies Michelle K. Demos Amy Goldman Harinder Gill Rachel Horton Bronwyn Kerr Dhavendra Kumar Anna Lehman Shane McKee Jenny Morton Michael J. Parker Julia Rankin Siddharth Banka 《American journal of human genetics》2018,102(1):175-187
29.
Copper-induced trafficking of the Cu-ATPases: A key mechanism for copper homeostasis 总被引:3,自引:0,他引:3
Julian F.B. Mercer Natalie Barnes Julie Stevenson Daniel Strausak Roxana M. Llanos 《Biometals》2003,16(1):175-184
The Menkes protein (MNK) and Wilson protein (WND) are transmembrane, CPX-type Cu-ATPases with six metal binding sites (MBSs) in the N-terminal region containing the motif GMXCXXC. In cells cultured in low copper concentration MNK and WND localize to the transGolgi network but in high copper relocalize either to the plasma membrane (MNK) or a vesicular compartment (WND). In this paper we investigate the role of the MBSs in Cu-transport and trafficking. The copper transport activity of MBS mutants of MNK was determined by their ability to complement a strain of Saccharomyces cerevisiae deficient in CCC2 (ccc2), the yeast MNK/WND homologue. Mutants (CXXC to SXXS) of MBS1, MBS6, and MBSs1-3 were able to complement ccc2 while mutants of MBS4-6, MBS5-6 and all six MBS inactivated the protein. Each of the inactive mutants also failed to display Cu-induced trafficking suggesting a correlation between trafficking and transport activity. A similar correlation was found with mutants of MNK in which various MBSs were deleted, but two constructs with deletion of MBS5-6 were unable to traffic despite retaining 25% of copper transport activity. Chimeras in which the N-terminal MBSs of MNK were replaced with the corresponding MBSs of WND were used to investigate the region of the molecules that is responsible for the difference in Cu-trafficking of MNK and WND. The chimera which included the complete WND N-terminus localized to a vesicular compartment, similar to WND in elevated copper. Deletions of various MBSs of the WND N-terminus in the chimera indicate that a targeting signal in the region of MBS6 directs either WND/MNK or WND to a vesicular compartment of the cell. 相似文献
30.
EST-based gene discovery in pig: virtual expression patterns and comparative mapping to human 总被引:3,自引:0,他引:3
Christopher K. Tuggle Jon A. Green Carolyn Fitzsimmons Rami Woods Randall S. Prather Sergei Malchenko Bento M. Soares Tamara Kucaba Keith Crouch Christina Smith Dylan Tack Natalie Robinson Brian O'Leary Todd Scheetz Thomas Casavant Daniel Pomp Brad J. Edeal Yuandan Zhang Max F. Rothschild Kevin Garwood William Beavis 《Mammalian genome》2003,14(8):565-579
A molecular understanding of porcine reproduction is of biological interest and economic importance. Our Midwest Consortium has produced cDNA libraries containing the majority of genes expressed in major female reproductive tissues, and we have deposited into public databases 21,499 expressed sequence tag (EST) gene sequences from the 3 end of clones from these libraries. These sequences represent 10,574 different genes, based on sequence comparison among these data, and comparison with existing porcine ESTs and genes indicate as many as 4652 of these EST clusters are novel. In silico analysis identified sequences that are expressed in specific pig tissues or organs and confirmed the broad expression in pig for many genes ubiquitously expressed in human tissues. Furthermore, we have developed computer software to identify sequence similarity of these pig genes with their human counterparts, and to extract the mapping information of these human homologues from genome databases. We demonstrate the utility of this software for comparative mapping by localizing 61 genes on the porcine physical map for Chromosomes (Chrs) 5, 10, and 14.
The following Accession numbers were assigned to our deposited sequences: BF701840 – BF704551, BF708383, BF708386 – BF713604, BG322266 – BG322271, BI398567 – BI405235, BQ597354 – BQ605166. 相似文献