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31.
Steele-Mortimer O Brumell JH Knodler LA Méresse S Lopez A Finlay BB 《Cellular microbiology》2002,4(1):43-54
Type III secretion systems (TTSS) are used by Gram-negative pathogens to translocate proteins into eukaryotic host cells. Salmonella enterica serovar Typhimurium (S. Typhimurium) has two of these specialized systems, which are encoded on separate Salmonella pathogenicity islands (SPI-1 and SPI-2) and translocate unique sets of effectors. The specific roles of these systems in Salmonella pathogenesis remain undefined, although SPI-1 is required for bacterial invasion of epithelial cells and SPI-2 for survival/replication in phagocytic cells. However, because SPI-1 TTSS mutants are invasion-incompetent, the role of this TTSS in post-invasion processes has not been investigated. In this study, we have used two distinct methods to internalize a non-invasive SPI-1 TTSS mutant (invA) into cultured epithelial cells: (i) co-internalization with wild-type S. Typhimurium (SPI-1-dependent) and (ii) complementation with the Yersinia pseudotuberculosis invasin (inv) gene (SPI-1-independent). In both cases, internalized invA mutants were unable to replicate intracellularly, indicating that SPI-1 effectors are essential for this process and cannot be complemented by wild-type bacteria in the same cell. Analysis of the biogenesis of SCVs showed that vacuoles containing mutant bacteria displayed abnormal maturation that was dependent on the mechanism of entry. Manipulation of Salmonella-containing vacuole (SCV) biogenesis by pharmacologically perturbing membrane trafficking in the host cell increased intracellular replication of wild-type but not mutant S. Typhimurium This demonstrates a previously unknown role for SPI-1 in vacuole biogenesis and intracellular survival in non-phagocytic cells. 相似文献
32.
Scott MG Rosenberger CM Gold MR Finlay BB Hancock RE 《Journal of immunology (Baltimore, Md. : 1950)》2000,165(6):3358-3365
33.
Eric W. Ainscough Andrew M. Brodie William A. Denny Graeme J. Finlay John D. Ranford 《Journal of inorganic biochemistry》1998,70(3-4):175-185
The preparation of N-, S- and O-donor ligand adducts with CuX+(HX=6-methyl-2-formylpyridinethiosemicarbazone (6HL); 2-formylpyridine-2′-methylthiosemicarbazone (2′L); 2-formylpyridine-4′-methylthiosemicarbazone (4′HL)) is described. The N-donors, 2,2′-bipyridyl (bipy), 4-dimethylaminopyridine (dmap) give the complexes [Cu(6L)(bipy)]PF6, [Cu(6L)(bipy)]Cl·5H2O, [Cu(4′L)(bipy)]PF6, [Cu(6L)(dmap)2]PF6·2.5 H2O and [Cu(4′L)(dmap)2]PF6·H2O which have been characterized by physical and spectroscopic techniques. Pentafluorothiophenolate (pftp) gives S-donor complexes [CuX(pftp)] (X=6L and 4′L) and thiolato co-ordination is proposed on the basis of spectroscopic evidence. Paratritylphenolate (ptp) and HPO2−4 give O-donor complexes [Cu(6L)(ptp)], [Cu(4′L)(ptp)], [{Cu(6L)}2HPO4]·4H2O, and [{Cu(4′L)}2HPO4]·5H2O which have been characterized by physical and spectroscopic techniques, as have the precursor complexes [Cu(6L)(CH3COO)]·H2O, [Cu(4′L)(CH3COO)], Cu(6HL)(CF3COO)](CF3COO)·0.5H2O, [Cu(4′HL)(CF3COO)](CF3COO), [Cu(2′L)Cl2] and [Cu(2′L)(NO3)2]. Protonation constants for the ligands and some of their complexes have been determined. 2-Formylpyridinethiosemicarbazone (HL) complexes of silver, gold, zinc, mercury, cadmium and lead are also discussed. Cytotoxicity against the human tumor cell line HCT-8 and antiviral data for selected compounds are presented. 相似文献
34.
35.
Inhibition of in vitro nuclear transport by a lectin that binds to nuclear pores 总被引:46,自引:42,他引:46 下载免费PDF全文
Selective transport of proteins is a major mechanism by which biochemical differences are maintained between the cytoplasm and nucleus. To begin to investigate the molecular mechanism of nuclear transport, we used an in vitro transport system composed of a Xenopus egg extract, rat liver nuclei, and a fluorescently labeled nuclear protein, nucleoplasmin. With this system, we screened for inhibitors of transport. We found that the lectin, wheat germ agglutinin (WGA), completely inhibits the nuclear transport of fluorescently labeled nucleoplasmin. No other lectin tested affected nuclear transport. The inhibition by WGA was not seen when N-acetylglucosamine was present and was reversible by subsequent addition of sugar. When rat liver nuclei that had been incubated with ferritin-labeled WGA were examined by electron microscopy, multiple molecules of WGA were found bound to the cytoplasmic face of each nuclear pore. Gel electrophoresis and nitrocellulose transfer identified one major and several minor nuclear protein bands as binding 125I-labeled WGA. The most abundant protein of these, a 63-65-kD glycoprotein, is a candidate for the inhibitory site of action of WGA on nuclear protein transport. WGA is the first identified inhibitor of nuclear protein transport and interacts directly with the nuclear pore. 相似文献
36.
Russell SL Gold MJ Hartmann M Willing BP Thorson L Wlodarska M Gill N Blanchet MR Mohn WW McNagny KM Finlay BB 《EMBO reports》2012,13(5):440-447
Allergic asthma rates have increased steadily in developed countries, arguing for an environmental aetiology. To assess the influence of gut microbiota on experimental murine allergic asthma, we treated neonatal mice with clinical doses of two widely used antibiotics--streptomycin and vancomycin--and evaluated resulting shifts in resident flora and subsequent susceptibility to allergic asthma. Streptomycin treatment had little effect on the microbiota and on disease, whereas vancomycin reduced microbial diversity, shifted the composition of the bacterial population and enhanced disease severity. Neither antibiotic had a significant effect when administered to adult mice. Consistent with the 'hygiene hypothesis', our data support a neonatal, microbiota-driven, specific increase in susceptibility to experimental murine allergic asthma. 相似文献
37.
38.
B L Finlay 《Journal of neurobiology》1992,23(9):1159-1171
Regional variations in cell death are ubiquitous in the nervous system. In the retina, cell death in retinal ganglion cells is elevated in the retinal periphery and may be important in setting up the initial conditions that produce central retinal specializations such as an area centralis or visual streak. In central visual system structures, pronounced spatial and spatiotemporal inhomogeneities in cell death are seen both in layers and regions of the lateral geniculate nucleus and superior colliculus; similar indications of inhomogeneities are seen in those nonvisual structures that have been examined. Cell death in the cortex is highly nonuniform, by layer and by cortical area. A variety of possible functions for these regional losses are proposed, in the context of a uniform mechanism for cell death that allows it to assume multiple functions. 相似文献
39.
Cynthia Wu Michael Sean McMurtry Roopinder K. Sandhu Erik Youngson Justin A. Ezekowitz Padma Kaul Finlay A. McAlister 《PloS one》2015,10(10)
Background and Purpose
We studied whether anticoagulant use and outcomes differed between rural versus urban Canadian non-valvular atrial fibrillation (NVAF) patients prior to the introduction of direct oral anticoagulant drugs.Methods
Retrospective cohort study of 25,284 adult Albertans with NVAF between April 1, 1999 and December 31, 2008.Results
Compared to urban patients, rural patients were older (p = 0.0009) and had more comorbidities but lower bleeding risk at baseline. In the first year after NVAF diagnosis, urban patients were less likely to be hospitalized (aOR 0.82, 95%CI 0.77–0.89) or have an emergency department visit for any reason (aOR 0.61, 95%CI 0.56–0.66) but warfarin dispensation rates (72.2% vs 71.8% at 365 days, p = 0.98) and clinical outcomes were similar: 7.8% died in both groups, 3.2% rural vs. 2.8% urban had a stroke or systemic embolism (SSE) (aOR 0.92, 95%CI 0.77–1.11), and 6.6% vs. 5.7% (aOR 0.93, 95%CI 0.81–1.06) had a bleed. Baseline SSE risk did not impact warfarin dispensation (73.0% in those with high vs. 72.8% in those with low CHADS2 score, p = 0.85) but patients at higher baseline bleeding risk were less likely to be using warfarin (69.2% high vs. 73.6% low HASBLED score, p<0.0001) in the first 365 days after diagnosis. In warfarin users, bleeding was more frequent (7.5% vs 6.2%, aHR 1.51 [95%CI 1.33–1.72]) but death or SSE was less frequent (7.0% vs 18.1%, aHR 0.60 [0.54–0.66]).Conclusion
Warfarin use and clinical event rates did not differ between rural and urban NVAF patients in a universal access publically-funded healthcare system. 相似文献40.