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Nerve growth factor (NGF) promotes angiogenesis in the quail chorioallantoic membrane. 总被引:1,自引:0,他引:1
Philip Lazarovici Aviv Gazit Izabela Staniszewska Cezary Marcinkiewicz Peter I Lelkes 《Endothelium》2006,13(1):51-59
Angiogenesis, the formation of new blood vessels, is tightly regulated by growth factors, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). The authors hypothesize that nerve growth factor (NGF), a well known neurotrophin, may play a direct angiogenic role. To test this hypothesis, the authors measured the effects of NGF on the natural vascularization of the quail chorioallantoic membrane (CAM). The angiogenic effect of NGF was compared to that of human recombinant VEGF165 (rhVEGF) and basic FGF (rhbFGF). In comparison to phosphate-buffered saline-treated controls, NGFs from different biological sources (mouse, viper, and cobra) increased the rate of angiogenesis in a dose-dependent fashion from 0.5 to 5 microg. For quantitative morphometry, grayscale images of the blood vessels end points of the CAM arteries were binarized for visualization and skeletonized for quantization by fractal analysis. In mouse NGF-treated embryos the fractal dimension (Df), indicative of arterial vessel length and density, increased to 1.266 +/- 0.021 compared to 1.131 +/- 0.018 (p < .001) for control embryos. This effect was similar to that of 0.5 microg rhVEGF (1.290 +/- 0.021, p < .001) and 1.5 microg rhbFGF (1.264 +/- 0.028, p < .001). The mouse NGF-induced angiogenic effect was blocked by 1 microM K252a (1.149 +/- 0.018, p < .001), an antagonist of the NGF/trkA receptor, but not by 1 microM SU-5416 (1.263 +/- 0.029, p < .001), the VEGF/Flk1 receptor antagonist, indicating a direct, selective angiogenic effect of NGF via quail embryo trkA receptor activation. These results confirm previous observations that NGF has angiogenic activity and suggest that this neurotrophin may also play an important role in the cardiovascular system, besides its well-known effects in the nervous system. The angiogenic properties of NGF may be beneficial in engineering new blood vessels and for developing novel antiangiogenesis therapies for cancer. 相似文献
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E Behar H Carp A Livneh E Gazit 《American journal of reproductive immunology (New York, N.Y. : 1989)》1991,26(4):143-146
In order to investigate the role of the idiotypic network in miscarriages, sera from 28 habitually aborting women undergoing paternal leukocyte immunization were studied for the presence of HLA antibodies and related anti-idiotypes. Sixty-eight percent of sera from preimmunized patients which did not contain anti-lymphocyte antibodies inhibited the activity of antibodies to the HLA class I antigens expressed by the spouse. This inhibitory activity could be assigned to IgM antibodies, which cross-inhibit antibodies of similar specificity. This suggests that they are anti-idiotypes for the binding site of HLA antibodies. Immune sera of successfully treated patients exhibited both cytotoxic IgG anti-HLA antibodies and inhibitory IgM anti-idiotypic antibodies. A possible role for an intact idiotypic network in maintaining pregnancy is suggested. 相似文献
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George J Barshack I Keren P Gazit A Levitzki A Keren G Roth A 《Experimental and molecular pathology》2005,78(3):233-238
BACKGROUND: Inflammation has been shown to play an important role in promoting the response to arterial injury and proinflammatory cytokines, such as tumor necrosis factor (TNF) alpha, are candidate mediators. AG-556 is a tyrosine kinase inhibitor proven to be effective in a model of multiple sclerosis-like syndrome in mice due to its immunomodulating effect. In the current study, we investigated the effect of the tyrphostin AG-556 on neointimal thickening and cytokine profile in a model of arterial injury in the mouse. METHODS: Injury was induced by external cuff placement on the left femoral artery of wild-type C57BL/6 mice. AG-556 dissolved in DMSO was injected intraperitoneally daily to the injured mice in a dosage of 2 mg/mouse. Control mice received DMSO injections. Histological analysis was carried out to assess neointimal formation. Splenocytes were cultured in the absence and presence of a mitogen for evaluation of thymidine incorporation and cytokine production. RESULTS: AG-556 treatment significantly attenuated intimal thickening (43,000+/-17,000 microm2; n=11) when compared to DMSO administration (286,000+/-127,000 microm2; n=10; P<0.05). Basal interferon-gamma production by splenocytes from AG-556-treated mice was increased by approximately 20-fold in comparison with levels in DMSO-treated animals, whereas Con-A induced secretion of the cytokine was similar between both groups. Levels of TNF-alpha, IL-4 and IL-10 in the culture supernatant from treated and non-treated animals did not differ significantly. CONCLUSION: The tyrosine kinase inhibitor AG-556 may have a role in the reduction of intimal thickening. The effect could be mediated via an immune modulating effect involving a significant increase in the smooth muscle cell inhibitory cytokine IFN-gamma. 相似文献
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Molecular clones of the integrated form of the genome of equine infectious anemia virus (EIAV), the etiologic agent of a naturally occurring, worldwide disease of horses, were obtained. The restriction map of a full-length genome was determined. Additional evidence for the close evolutionary relationship between EIAV and a prototype lentivirus (caprine arthritis encephalitis virus) was acquired by Southern blotting and immunological analyses. An interspecies radioimmunoassay was developed in which EIAV and ovine and caprine lentiviruses could be detected equally well. These studies make available precisely defined reagents to pursue the study of the mechanisms of pathogenesis of lentiviral induced diseases. 相似文献
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Baruch Kunievsky Ephraim Yavin Ph.D. 《Molecular and chemical neuropathology / sponsored by the International Society for Neurochemistry and the World Federation of Neurology and research groups on neurochemistry and cerebrospinal fluid》1990,13(1-2):155-163
Intact cerebral hemispheres from 20-d-old rat fetuses incubated at 37°C in Dulbecco’s Modified Eagle Medium (DMEM) synthesize and release a number of arachidonic acid derived metabolites, such as thromboxane B2 (TxB2), 6-keto prostaglandin F1α (6k-PGF1α), and prostaglandin E2 (PGE2) eicosanoids. Synthesis is time-dependent and is stimulated upon addition of the calcium ionophore A23187(10 μM). Ionophore stimulation is prevented by EDTA/EGTA (5 mM each) ion chelators, dextran-70 (5%), and indomethacin (10 μM), a potent cyclooxygenase inhibitor. Ca2+ (2 mM) enhances ionophoremediated formation of TxB2, 6K-PGF1α, and PGE2 by 2.5-, 2.9-, and 4.2-fold, respectively; Mg2+ blocks ionophore stimulation. Freezing and thawing enhances release of eicosanoids to a level nearly the same as that obtained in the presence of A23187, indicating a common mode of action. 相似文献
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