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Rong Chen Alex A Morgan Joel Dudley Tarangini Deshpande Li Li Keiichi Kodama Annie P Chiang Atul J Butte 《Genome biology》2009,9(12):R170
Background
Candidate single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWASs) were often selected for validation based on their functional annotation, which was inadequate and biased. We propose to use the more than 200,000 microarray studies in the Gene Expression Omnibus to systematically prioritize candidate SNPs from GWASs. 相似文献114.
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T Deshpande T Takagi L Hao S Buratowski H Charbonneau 《The Journal of biological chemistry》1999,274(23):16590-16594
A human cDNA was isolated encoding a protein with significant sequence similarity (41% identity) to the BVP RNA 5'-phosphatase from the Autographa californica nuclear polyhedrosis virus. This protein is a member of the protein-tyrosine phosphatase (PTP) superfamily and is identical to PIR1, shown by Yuan et al. (Yuan, Y., Da-Ming, L., and Sun, H. (1998) J. Biol. Chem. 272, 20347-20353) to be a nuclear protein that can associate with RNA or ribonucleoprotein complexes. We demonstrate that PIR1 removes two phosphates from the 5'-triphosphate end of RNA, but not from mononucleotide triphosphates. The specific activity of PIR1 with RNA is several orders of magnitude greater than that with the best protein substrates examined, suggesting that RNA is its physiological substrate. A 120-amino acid segment C-terminal to the PTP domain is not required for RNA phosphatase activity. We propose that PIR1 and its closest homologs, which include the metazoan mRNA capping enzymes, constitute a subgroup of the PTP family that use RNA as a substrate. 相似文献
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Venkat R. Gadhachanda Kyle J. Eastman Qiuping Wang Avinash S. Phadke Dharaben Patel Wengang Yang Christopher W. Marlor Milind Deshpande Mingjun Huang Jason A. Wiles 《Bioorganic & medicinal chemistry letters》2018,28(21):3463-3471
An unprecedented series of organometallic HCV (hepatitis C virus) NS5A (nonstructural 5A protein) replication complex inhibitors that incorporates a 1,1′-ferrocenediyl scaffold was explored. This scaffold introduces the elements of linear flexibility and non-planar topology that are unconventional for this class of inhibitors. Data from 2-D NMR spectroscopic analyses of these complexes in solution support an anti (unstacked) arrangement of the pharmacophoric groups. Several complexes demonstrate single-digit picomolar in vitro activity in an HCV genotype-1b replicon system. One complex to arise from this investigation (10a) exhibits exceptional picomolar activity against HCV genotype 1a and 1b replicons, low hepatocellular cytotoxicity, and good pharmacokinetic properties in rat. 相似文献
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L-Lactate dehydrogenase (L-LDH, E.C. 1.1.1.27) is encoded by two or three
loci in all vertebrates examined, with the exception of lampreys, which
have a single LDH locus. Biochemical characterizations of LDH proteins have
suggested that a gene duplication early in vertebrate evolution gave rise
to Ldh-A and Ldh-B and that an additional locus, Ldh-C arose in a number of
lineages more recently. Although some phylogenetic studies of LDH protein
sequences have supported this pattern of gene duplication, others have
contradicted it. In particular, a number of studies have suggested that
Ldh-C represents the earliest divergence among vertebrate LDHs and that it
may have diverged from the other loci well before the origin of
vertebrates. Such hypotheses make explicit statements about the
relationship of vertebrate and invertebrate LDHs, but to date, no closely
related invertebrate LDH sequences have been available for comparison. We
have attempted to provide further data on the timing of gene duplications
leading to multiple vertebrate LDHs by determining the cDNA sequence of the
LDH of the tunicate Styela plicata. Phylogenetic analyses of this and other
LDH sequences provide strong support for the duplications giving rise to
multiple vertebrate LDHs having occurred after vertebrates diverged from
tunicates. The timing of these LDH duplications is consistent with data
from a number of other gene families suggesting widespread gene duplication
near the origin of vertebrates. With respect to the relationships among
vertebrate LDHs, our data are not consistent with previous claims that
Ldh-C represented the earliest divergence. However, the precise
relationships among some of the main lineages of vertebrate LDHs were not
resolved in our analyses.
相似文献
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