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911.
Frederic Dalle Betty Wchtler Coralie L'Ollivier Gudrun Holland Norbert Bannert Duncan Wilson Catherine Labrure Alain Bonnin Bernhard Hube 《Cellular microbiology》2010,12(2):248-271
The human pathogenic fungus Candida albicans can cause systemic infections by invading epithelial barriers to gain access to the bloodstream. One of the main reservoirs of C. albicans is the gastrointestinal tract and systemic infections predominantly originate from this niche. In this study, we used scanning electron and fluorescence microscopy, adhesion, invasion and damage assays, fungal mutants and a set of fungal and host cell inhibitors to investigate the interactions of C. albicans with oral epithelial cells and enterocytes. Our data demonstrate that adhesion, invasion and damage by C. albicans depend not only on fungal morphology and activity, but also on the epithelial cell type and the differentiation stage of the epithelial cells, indicating that epithelial cells differ in their susceptibility to the fungus. C. albicans can invade epithelial cells by induced endocytosis and/or active penetration. However, depending on the host cell faced by the fungus, these routes are exploited to a different extent. While invasion into oral cells occurs via both routes, invasion into intestinal cells occurs only via active penetration. 相似文献
912.
913.
Gerald J. Wilmink Caleb L. Roth Bennett L. Ibey Norma Ketchum Joshua Bernhard Cesario Z. Cerna William P. Roach 《Cell stress & chaperones》2010,15(6):1027-1038
MicroRNAs (miRNAs) are a class of small RNAs that play a critical role in the coordination of fundamental cellular processes.
Recent studies suggest that miRNAs participate in the cellular stress response (CSR), but their specific involvement remains
unclear. In this study, we identify a group of thermally regulated miRNAs (TRMs) that are associated with the CSR. Using miRNA
microarrays, we show that dermal fibroblasts differentially express 123 miRNAs when exposed to hyperthermia. Interestingly,
only 27 of these miRNAs are annotated in the current Sanger registry. We validated the expression of the annotated miRNAs
using qPCR techniques, and we found that the qPCR and microarray data was in well agreement. Computational target-prediction
studies revealed that putative targets for the TRMs are heat shock proteins and Argonaute-2—the core functional unit of RNA
silencing. These results indicate that cells express a specific group of miRNAs when exposed to hyperthermia, and these miRNAs
may function in the regulation of the CSR. Future studies will be conducted to determine if other cells lines differentially
express these miRNAs when exposed to hyperthermia. 相似文献
914.
915.
Background
A non-adaptive radiation triggered by sexual selection resulted in ten endemic land snail species of the genus Xerocrassa on Crete. Only five of these species and a more widespread species are monophyletic in a mitochondrial gene tree. The reconstruction of the evolutionary history of such closely related species can be complicated by incomplete lineage sorting, introgression or inadequate taxonomy. To distinguish between the reasons for the nonmonophyly of several species in the mitochondrial gene tree we analysed nuclear AFLP markers. 相似文献916.
Krämer EA Seeger H Krämer B Wallwiener D Mueck AO 《The Journal of steroid biochemistry and molecular biology》2006,98(2-3):174-178
OBJECTIVE: Evidence is increasing that adding progestogens to hormone replacement therapy may be more harmful than beneficial, however it is debatable whether all progestogens act equally on breast cells. Mitogenic growth factors from stromal breast tissue are important in growth-regulation of breast cells, and may modify responses to progestogens. We investigated the effect of two C-21 derivatives, medroxyprogesterone acetate (MPA) and chlormadinone acetate (CMA) on growth-factor treated normal breast epithelial cells and tried to explore the underlying mechanisms of proliferation. METHOD: MCF10A (human epithelial, estrogen- and progesterone-receptor negative normal breast cells) were incubated with MPA or CMA at 0.1 and 1 microM for 7 days with the growth factors (GFs) EGF, bFGF and IGF-I at 1pM. The same combinations, as well as growth factors alone, were also incubated with the proliferation inhibitors PD98059 and LY294002 at 1 microM for 4 days. Cell proliferation rate was measured by the ATP-assay. RESULTS: MPA 0.1 and 1 microM, and CMA 1 microM in combination with GFs both significantly increased cell proliferation rate, with MPA having the greatest effect. MPA- and CMA-induced proliferation of GF stimulated cells was blocked by both PD98059 (selective inhibitor of MAP kinases) and LY294002 (phosphatidylinositol 3-kinase inhibitor); GF stimulated cells could not be significantly reduced by any of the inhibitors used. CONCLUSION: MPA and CMA have a stimulatory effect on benign growth factor stimulated MCF10A cells, possibly via activation of MAP kinase and subsequent substrates and activation of PI3-kinase. GF induced proliferation appear to be mediated by pathways other than those investigated here. Growth factors and progestogens therefore have an additive, synergistic effect on cell proliferation, eliciting their effects via different pathways. 相似文献
917.
Hoffmann T Bös M Stadler H Schnider P Hunkeler W Godel T Galley G Ballard TM Higgins GA Poli SM Sleight AJ 《Bioorganic & medicinal chemistry letters》2006,16(5):1362-1365
The discovery of a novel, achiral pyridine class of potent and orally active neurokinin-1 (NK(1)) receptor antagonists is described. The evaluation of this class is briefly outlined, leading to the identification of netupitant 21 and befetupitant 29, two new proprietary chemical entities with high affinity and excellent CNS penetration. 相似文献
918.
Monien BH Henry BL Raghuraman A Hindle M Desai UR 《Bioorganic & medicinal chemistry》2006,14(23):7988-7998
Thrombin and factor Xa, two important procoagulant enzymes, have been prime targets for regulation of clotting through the direct and indirect mechanism of inhibition. Our efforts on exploiting the indirect mechanism led us to study a carboxylic acid-based scaffold, which displayed major acceleration in the inhibition of these enzymes [J. Med. Chem.2005, 48, 1269, 5360]. This work advances the study to chemo-enzymatically prepared oligomers of 4-hydroxycinnamic acids, DHPs, which display interesting anticoagulant properties. Oligomers, ranging in size from tetramers to pentadecamers, were prepared through peroxidase-catalyzed oxidative coupling of caffeic, ferulic, and sinapic acids, and sulfated using triethylamine-sulfur trioxide complex. Chromatographic, spectroscopic, and elemental studies suggest that the DHPs are heterogeneous, polydisperse preparations composed of inter-monomer linkages similar to those found in natural lignins. Measurement of activated thromboplastin and prothrombin time indicates that both the sulfated and unsulfated derivatives of the DHPs display anticoagulant activity, which is dramatically higher than that of the reference polyacrylic acids. More interestingly, this activity approaches that of low-molecular-weight heparin with the sulfated derivative showing approximately 2- to 3-fold greater potency than the unsulfated parent. Studies on the inhibition of factor Xa and thrombin indicate that the oligomers exert their anticoagulant effect through both direct and indirect inhibition mechanisms. This dual inhibition property of 4-hydroxycinnamic acid-based DHP oligomers is the first example in inhibitors of coagulation. This work puts forward a novel, non-heparin structure, which may be exploited for the design of potent, dual action inhibitors of coagulation through combinatorial virtual screening on a library of DHP oligomers. 相似文献
919.
Mitochondrial genomes provide a valuable dataset for phylogenetic studies, in particular of metazoan phylogeny because of the extensive taxon sample that is available. Beyond the traditional sequence-based analysis it is possible to extract phylogenetic information from the gene order. Here we present a novel approach utilizing these data based on cyclic list alignments of the gene orders. A progressive alignment approach is used to combine pairwise list alignments into a multiple alignment of gene orders. Parsimony methods are used to reconstruct phylogenetic trees, ancestral gene orders, and consensus patterns in a straightforward approach. We apply this method to study the phylogeny of protostomes based exclusively on mitochondrial genome arrangements. We, furthermore, demonstrate that our approach is also applicable to the much larger genomes of chloroplasts. 相似文献
920.