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161.
Human susceptibility and resistance to Norwalk virus infection 总被引:27,自引:0,他引:27
Lindesmith L Moe C Marionneau S Ruvoen N Jiang X Lindblad L Stewart P LePendu J Baric R 《Nature medicine》2003,9(5):548-553
Infectious diseases have influenced population genetics and the evolution of the structure of the human genome in part by selecting for host susceptibility alleles that modify pathogenesis. Norovirus infection is associated with approximately 90% of epidemic non-bacterial acute gastroenteritis worldwide. Here, we show that resistance to Norwalk virus infection is multifactorial. Using a human challenge model, we showed that 29% of our study population was homozygous recessive for the alpha(1,2)fucosyltransferase gene (FUT2) in the ABH histo-blood group family and did not express the H type-1 oligosaccharide ligand required for Norwalk virus binding. The FUT2 susceptibility allele was fully penetrant against Norwalk virus infection as none of these individuals developed an infection after challenge, regardless of dose. Of the susceptible population that encoded a functional FUT2 gene, a portion was resistant to infection, suggesting that a memory immune response or some other unidentified factor also affords protection from Norwalk virus infection. 相似文献
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Brandon LD Goehring N Janakiraman A Yan AW Wu T Beckwith J Goldberg MB 《Molecular microbiology》2003,50(1):45-60
Asymmetric localization of proteins is essential to many biological functions of bacteria. Shigella IcsA, an outer membrane protein, is localized to the old pole of the bacillus, where it mediates assembly of a polarized actin tail during infection of mammalian cells. Actin tail assembly provides the propulsive force for intracellular movement and intercellular dissemination. Localization of IcsA to the pole is independent of the amino-terminal signal peptide (Charles, M., Perez, M., Kobil, J.H., and Goldberg, M.B., 2001, Proc Natl Acad Sci USA 98: 9871-9876) suggesting that IcsA targeting occurs in the bacterial cytoplasm and that its secretion across the cytoplasmic membrane occurs only at the pole. Here, we characterize the mechanism by which IcsA is secreted across the cytoplasmic membrane. We present evidence that IcsA requires the SecA ATPase and the SecYEG membrane channel (translocon) for secretion. Our data suggest that YidC is not required for IcsA secretion. Furthermore, we show that polar localization of IcsA is independent of SecA. Finally, we demonstrate that while IcsA requires the SecYEG translocon for secretion, components of this apparatus are uniformly distributed within the membrane. Based on these data, we propose a model for coordinate polar targeting and secretion of IcsA at the bacterial pole. 相似文献
165.
Xu J Zheng SL Chang B Smith JR Carpten JD Stine OC Isaacs SD Wiley KE Henning L Ewing C Bujnovszky P Bleeker ER Walsh PC Trent JM Meyers DA Isaacs WB 《Human genetics》2001,108(4):335-345
Three prostate cancer susceptibility genes have been reported to be linked to different regions on chromosome 1: HPC1 at 1q24-25, PCAP at 1q42-43, and CAPB at 1p36. Replication studies analyzing each of these regions have yielded inconsistent results. To evaluate linkage across this chromosome systematically, we performed multipoint linkage analyses with 50 microsatellite markers spanning chromosome 1 in 159 hereditary prostate cancer families (HPC), including 79 families analyzed in the original report describing HPC1 linkage. The highest lod scores for the complete dataset of 159 families were observed at 1q24-25 at which the parametric lod score assuming heterogeneity (hlod) was 2.54 (P=0.0006) with an allele sharing lod of 2.34 (P=0.001) at marker D1S413, although only weak evidence was observed in the 80 families not previously analyzed for this region (hlod=0.44, P=0.14, and allele sharing lod=0.67, P=0.08). In the complete data set, the evidence for linkage across this region was very broad, with allele sharing lod scores greater than 0.5 extending approximately 100 cM from 1p13 to 1q32, possibly indicating the presence of multiple susceptibility genes. Elsewhere on chromosome 1, some evidence of linkage was observed at 1q42-43, with a peak allele sharing lod of 0.56 (P=0.11) and hlod of 0.24 (P=0.25) at D1S235. For analysis of the CAPB locus at 1p36, we focused on six HPC families in our collection with a history of primary brain cancer; four of these families had positive linkage results at 1p36, with a peak allele sharing lod of 0.61 (P=0.09) and hlod of 0.39 (P=0.16) at D1S407 in all six families. These results are consistent with the heterogeneous nature of hereditary prostate cancer, and the existence of multiple loci on chromosome 1 for this disease. 相似文献
166.
LC-NMR: a new tool to expedite the dereplication and identification of natural products 总被引:1,自引:0,他引:1
The rapid identification of known or undesirable compounds from natural products extracts — “dereplication” — is an important
step in an efficiently run natural products discovery program. Dereplication strategies use analytical techniques and database
searching to determine the identity of an active compound at the earliest possible stage in the discovery process. In the
past few years, advances in technology have allowed the development of tandem analytical techniques such as liquid chromatography
mass spectrometry (LC-MS), LC-MS-MS, liquid chromatography nuclear magnetic resonance (LC-NMR), and LC-NMR-MS. LC-NMR, despite
its lower sensitivity as compared to LC-MS, provides a powerful tool for rapid identification of known compounds and identification
of structure classes of novel compounds. LC-NMR is especially useful in instances where the data from LC-MS are incomplete
or do not allow confident identification of the active component of a sample. LC-NMR has been used to identify the marine
alkaloid aaptamine as the active component in an extract of the sponge Aaptos sp. This extract had been identified as an enzyme inhibitor by a high throughput screening (HTS) effort. Isolated aaptamine
exhibited an IC50=120 μM against this enzyme. Strategies for the identification of aaptamine and for the use of LC-NMR in a natural products
HTS program are discussed. Journal of Industrial Microbiology & Biotechnology (2000) 25, 342–345.
Received 30 March 2000/ Accepted in revised form 03 July 2000 相似文献
167.
Cell suspension cultures of Pinus radiata metabolize the antifungal Trichoderma secondary metabolite 6-n-pentyl-2H-pyran-2-one (6PAP) (1) via hydroxylation of the pentyl side chain. Examination of the culture medium following dosing studies with 1 revealed that 79-85% of this bioactive compound had been metabolised after 144 h. At that time, 34-40% of the metabolized dose was recovered as a series of monohydroxylated isomers of 1, the principal metabolite being 5-(2-pyron-6-yl)pentan-5-ol (7). 相似文献
168.
This study examines the relationship of profundal oxygen concentrations in 55 shallow Florida lakes to humic color, trophic
state, and lake size during different seasons. The data set represented a broad range of color and trophic state. The percent
saturation of dissolved oxygen remained relatively constant during the fall (mean 78.4%), winter (mean 81.3%), and spring
(mean 82.5%), but declined markedly during summer (mean 65.2%). Chlorophyll a concentrations were highest during the winter
(mean 2.52 mg m–3) and lowest during the fall (mean 1.17 mg m–3), while color peaked during the fall (mean 30.1 mg Pt l–1) and was lowest during the summer (mean 12.7 mg Pt l–1). The relative importance of lake size, chlorophyll a, and color in explaining variation in percent oxygen saturation was
examined using multiple regression. Percent oxygen saturation was negatively correlated with color during the winter, spring,
and summer, and positively correlated with lake size in the winter and spring. However, percent oxygen saturation showed no
relationship with chlorophyll a during any season. These results suggest that colored Florida lakes are naturally oxygen depleted
and that profundal oxygen values have little relationship to lake trophic state.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
169.
Regulation of Adherence and Virulence by the Entamoeba histolytica Lectin Cytoplasmic Domain, Which Contains a β2 Integrin Motif
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Richard R. Vines Girija Ramakrishnan Joshua B. Rogers Lauren A. Lockhart Barbara J. Mann William A. Petri Jr. 《Molecular biology of the cell》1998,9(8):2069-2079
Killing of human cells by the parasite Entamoeba histolytica requires adherence via an amebic cell surface lectin. Lectin activity in the parasite is regulated by inside-out signaling. The lectin cytoplasmic domain has sequence identity with a region of the β2 integrin cytoplasmic tail implicated in regulation of integrin-mediated adhesion. Intracellular expression of a fusion protein containing the cytoplasmic domain of the lectin has a dominant negative effect on extracellular lectin-mediated cell adherence. Mutation of the integrin-like sequence abrogates the dominant negative effect. Amebae expressing the dominant negative mutant are less virulent in an animal model of amebiasis. These results suggest that inside-out signaling via the lectin cytoplasmic domain may control the extracellular adhesive activity of the amebic lectin and provide in vivo demonstration of the lectin’s role in virulence. 相似文献
170.