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Beharka AA Crowther JE McCormack FX Denning GM Lees J Tibesar E Schlesinger LS 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(4):2227-2236
Surfactant protein A (SP-A), a major component of lung surfactant, binds to macrophages and has been shown to alter several macrophage biological functions, including up-regulation of macrophage mannose receptor (MR) activity. In the present study, we show that SP-A induces signal transduction pathway(s) that impact on MR expression. The addition of human, rat, or recombinant rat SP-A to human monocyte-derived macrophages significantly raised the level of cytosolic Ca2+ above baseline within 10 s of SP-A addition, as measured by spectrofluorometric analysis. SP-A induced a refractory state specific for SP-A consistent with homologous desensitization of a receptor(s) linked to calcium mobilization because a second application of SP-A did not induce a rise in cytosolic Ca2+ whereas the addition of platelet-activating factor did. Using site-directed mutations in SP-A, we determined that both the attached sugars and the collagen-like domain of SP-A are necessary to optimize Ca2+ mobilization. SP-A triggered the increase in cytosolic Ca2+ by inducing activation of phospholipase C, which leads to the hydrolysis of membrane phospholipids, yielding inositol 1,4,5-trisphosphate and mobilizing intracellularly stored Ca2+ by inositol triphosphate-sensitive channels. Finally, inhibition of PI3Ks, which appear to act upstream of phospholipase C in Ca2+ mobilization, decreased the SP-A-induced rise in MR expression, providing evidence that SP-A induction of MR activity involves the activation of a pathway in which PI3K is a component. These studies provide further evidence that SP-A produced in the lung plays a role in modulating macrophage biology, thereby contributing to the alternative activation state of the alveolar macrophage. 相似文献
214.
Brian?DM?TomEmail author Walter?R?Gilks Elizabeth?T?Brooke-Powell James?W?Ajioka 《BMC bioinformatics》2005,6(1):234
Background
A common feature of microarray experiments is the occurence of missing gene expression data. These missing values occur for a variety of reasons, in particular, because of the filtering of poor quality spots and the removal of undefined values when a logarithmic transformation is applied to negative background-corrected intensities. The efficiency and power of an analysis performed can be substantially reduced by having an incomplete matrix of gene intensities. Additionally, most statistical methods require a complete intensity matrix. Furthermore, biases may be introduced into analyses through missing information on some genes. Thus methods for appropriately replacing (imputing) missing data and/or weighting poor quality spots are required. 相似文献215.
Background
The taxonomic name of an organism is a key link between different databases that store information on that organism. However, in the absence of a single, comprehensive database of organism names, individual databases lack an easy means of checking the correctness of a name. Furthermore, the same organism may have more than one name, and the same name may apply to more than one organism. 相似文献216.
SMM?VerstappenEmail author AR?Poole M?Ionescu LE?King M?Abrahamowicz DM?Hofman JWJ?Bijlsma FPJG?Lafeber the Utrecht Rheumatoid Arthritis Cohort Study group 《Arthritis research & therapy》2005,8(1):R31
Introduction
The objective of this study was to determine whether serum biomarkers for degradation and synthesis of the extracellular matrix of cartilage are associated with, and can predict, radiographic damage in patients with rheumatoid arthritis (RA). 相似文献217.
Inglis JJ Nissim A Lees DM Hunt SP Chernajovsky Y Kidd BL 《Arthritis research & therapy》2005,7(4):R807-R816
Therapies directed against tumour necrosis factor (TNF) are effective for the treatment of rheumatoid arthritis and reduce
pain scores in this condition. In this study, we sought to explore mechanisms by which TNF contributes to inflammatory pain
in an experimental model of arthritis. The effects of an anti-TNF agent, etanercept, on behavioural pain responses arising
from rat monoarthritis induced by complete Freund's adjuvant were assessed and compared with expression of TNF receptors (TNFRs)
by dorsal root ganglion (DRG) cells at corresponding time points. Etanercept had no effect on evoked pain responses in normal
animals but exerted a differential effect on the thermal and mechanical hyperalgesia associated with rat arthritis induced
by complete Freund's adjuvant (CFA). Joint inflammation was associated with increased TNFR1 and TNFR2 expression on DRG cells,
which was maintained throughout the time course of the model. TNFR1 expression was increased in neuronal cells of the DRG
bilaterally after arthritis induction. In contrast, TNFR2 expression occurred exclusively on non-neuronal cells of the macrophage–monocyte
lineage, with cell numbers increasing in a TNF-dependent fashion during CFA-induced arthritis. A strong correlation was observed
between numbers of macrophages and the development of mechanical hyperalgesia in CFA-induced arthritis. These results highlight
the potential for TNF to play a vital role in inflammatory hyperalgesia, both by a direct action on neurons via TNFR1 and
by facilitating the accumulation of macrophages in the DRG via a TNFR2-mediated pathway. 相似文献
218.
A cryptococcal capsular polysaccharide mimotope prolongs the survival of mice with Cryptococcus neoformans infection 总被引:3,自引:0,他引:3
Defined Abs to the Cryptococcus neoformans capsular polysaccharide glucuronoxylomannan (GXM) have been shown to be protective against experimental cryptococcosis. This suggests that if a vaccine could induce similar Abs it might protect against infection. However, the potential use of a GXM-based vaccine has been limited by evidence that GXM is a poor immunogen that can induce nonprotective and deleterious, as well as protective, Abs, and that the nature of GXM oligosaccharide epitopes that can elicit a protective response is unknown. In this study, we investigated whether a peptide surrogate for a GXM epitope could induce an Ab response to GXM in mice. The immunogenicity of peptide-protein conjugates produced by linking a peptide mimetic of GXM, P13, to either BSA, P13-BSA, or tetanus toxoid, P13-tetanus toxoid, was examined in BALB/c and CBA/n mice that received four s.c. injections of the conjugates at 14- to 30-day intervals. All mice immunized with conjugate produced IgM and IgG to P13 and GXM. Challenge of conjugate-immunized mice with C. neoformans revealed longer survival and lower serum GXM levels than control mice. These results indicate that 1) P13 is a GXM mimotope and 2) that it induced a protective response against C. neoformans in mice. P13 is the first reported mimotope of a C. neoformans Ag. Therefore, the P13 conjugates are vaccine candidates for C. neoformans and their efficacy in this study suggests that peptide mimotopes selected by protective Abs deserve further consideration as vaccine candidates for encapsulated pathogens. 相似文献
219.
Examining monophyly in a large radiation of Madagascan butterflies (Lepidoptera: Satyrinae: Mycalesina) based on mitochondrial DNA data 总被引:5,自引:0,他引:5
Torres E Lees DC Vane-Wright RI Kremen C Leonard JA Wayne RK 《Molecular phylogenetics and evolution》2001,20(3):460-473
The satyrine butterfly subtribe Mycalesina has undergone one of the more spectacular evolutionary radiations of butterflies in the Old World tropics. Perhaps the most phenotypically pronounced diversification of the group has occurred in the Malagasy region, where 68 currently recognized species are divided among five genera. Here, we report the results of phylogenetic analyses of sequence data from the cytochrome c oxidase II and cytochrome b mitochondrial genes, for a total of 54 mycalesine taxa, mostly from Madagascar. These molecular data complement an existing data set based on male morphological characters. The molecular results support the suggestion from morphology that three of the five Malagasy genera are paraphyletic and support the monophyly of at least three major morphological clades. Novel hypotheses of terminal taxon pairs are generated by the molecular data. Dense taxon sampling appears to be crucial for elucidating phylogenetic relationships within this large radiation. A potentially complex scenario for the origin of Malagasy mycalesines is proposed. 相似文献
220.