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21.
Cyclooxygenase-2 activation mediates the proangiogenic effect of nitric oxide in colorectal cancer. 总被引:14,自引:0,他引:14
Fabio Cianchi Camillo Cortesini Ornella Fantappiè Luca Messerini Iacopo Sardi Nadia Lasagna Federico Perna Valentina Fabbroni Annamaria Di Felice Giuliano Perigli Roberto Mazzanti Emanuela Masini 《Clinical cancer research》2004,10(8):2694-2704
PURPOSE: Up-regulation of both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) enzymes has been reported in colorectal cancer. We aimed at evaluating the possible interaction between the nitric oxide and COX-2 pathways, and its effect on promoting tumor angiogenesis. EXPERIMENTAL DESIGN: Expression of iNOS, COX-2, vascular endothelial growth factor (VEGF), and CD31 was analyzed in tumor samples and corresponding normal mucosa obtained from 46 surgical specimens. We also evaluated iNOS activity, prostaglandin E(2) (PGE(2)), cyclic GMP and cyclic AMP production in the same specimens. Nitrite/nitrate levels, and PGE(2) and VEGF production were assessed in HCT116 and HT29 colon cancer cell lines after induction and selective inhibition of the two enzyme pathways. RESULTS: A significant correlation was found between iNOS and COX-2 immunohistochemical expression. PGE(2) production significantly correlated with iNOS activity and cGMP levels. A significant correlation was also found among PGE(2) production, microvessel density, and VEGF expression. Coinduction of both iNOS and COX-2 activities occurred after lipopolysaccharide (LPS) and epidermal growth factor (EGF) treatment in HCT116 and HT29 cells. Inhibition of iNOS by 1400W significantly reduced both LPS- and EGF-induced PGE(2) production. Treatment with LPS, EGF, and arachidonic acid significantly increased VEGF production in the iNOS-negative/COX-2-positive HT29 cells. This effect was completely reversed by treatment with the selective COX-2 inhibitor celecoxib. CONCLUSIONS: Our data showed a prominent role of nitric oxide in stimulating COX-2 activity in colorectal cancer. This interaction is likely to produce a cooperative effect in promoting angiogenesis through PGE(2)-mediated increase in VEGF production. 相似文献
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Gianni Sava Sonia Zorzet Claudia Turrin Francesca Vita MariaRosa Soranzo Giuliano Zabucchi Moreno Cocchietto Alberta Bergamo Stefano DiGiovine Gabriella Pezzoni Luigi Sartor Spiridione Garbisa 《Clinical cancer research》2003,9(5):1898-1905
NAMI-A is a ruthenium complex endowed with a selective effect on lung metastases of solid metastasizing tumors. The aim of this study is to provide evidence that NAMI-A's effect is based on the selective sensitivity of the metastasis cell, as compared with other tumor cells, and to show that lungs represent a privileged site for the antimetastatic effects. The transplantation of Lewis lung carcinoma cells, harvested from the primary tumor of mice treated with 35 mg/kg/day NAMI-A for six consecutive days, a dose active on metastases, shows no change in primary tumor take and growth but a significant reduction in formation of spontaneous lung metastases. Transmission electron microscopy examination of lungs and kidney shows NAMI-A to selectively bind collagen of the lung extracellular matrix and also type IV collagen of the basement membrane of kidney glomeruli. The half lifetime of NAMI-A elimination from the lungs is longer than for liver, kidney, and primary tumor. NAMI-A bound to collagen is active on tumor cells as shown in vitro by an invasion test, using a modified Boyden chamber and Matrigel, and it inhibits the matrix metallo-proteinases MMP-2 and MMP-9 at micromolar concentrations, as shown in vitro by a zimography test. These data show NAMI-A to significantly affect tumor cells with metastatic ability. Binding to collagen allows NAMI-A to exert its selective activity on metastatic cells during dissemination and particularly in the lungs. These data also stress the wide spectrum of daily doses and treatment schedules at which NAMI-A is active against metastases. 相似文献
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Antioxidant properties of ursodeoxycholic acid 总被引:5,自引:0,他引:5
Lapenna D Ciofani G Festi D Neri M Pierdomenico SD Giamberardino MA Cuccurullo F 《Biochemical pharmacology》2002,64(11):1661-1667
We have investigated potential antioxidant properties of the clinically relevant bile acid UDCA, which reaches therapeutic concentrations up to 0.09 and 29 mM, respectively, in human plasma and bile. UDCA was an excellent scavenger of OHz.rad; generated by FeCl(3)-EDTA, H(2)O(2) and ascorbate in the deoxyribose oxidation test, showing IC(min) and IC(50) values of 0.02 and 0.2 mM, respectively, and a second-order rate constant for reaction with OHz.rad; of 2+/-0.1 x 10(10)M(-1)s(-1). Notably, the drug could enhance at 1.5 mM concentration the antioxidant capacity of human bile against OHz.rad;-induced deoxyribose oxidation. UDCA also showed antioxidant effects in the deoxyribose test performed with nonchelated iron ions, such as Fe(2+) plus H(2)O(2) (IC(min): 7 mM, IC(50): 20 mM) or Fe(3+) plus H(2)O(2) and ascorbate (IC(min): 0.3 mM, IC(50): 5 mM), and inhibited ferrozine-Fe(2+) and desferrioxamine-Fe(3+) complexes formation with IC(50) values of, respectively, 12 and 0.3 mM, indicating that the drug interacts more with iron(III) than with iron(II). Moreover, UDCA significantly inhibited phospholipid liposome peroxidation induced by the OHz.rad;-generating system FeCl(3)-EDTA, H(2)O(2) and ascorbate (IC(min): 0.75 mM, IC(50): 3 mM), and by peroxyl radicals generated in the aqueous phase by AAPH (IC(min): 8 mM, IC(50): 14 mM). UDCA, even at 25 mM concentration, was ineffective on the lipoperoxidation mediated by Fe(2+) alone, but at the same concentration counteracted significantly that by Fe(3+) plus ascorbate, further pointing to its preferential antioxidant interaction with iron(III).In conclusion, UDCA has direct antioxidant properties, which are especially relevant against Fe(3+)- and OHz.rad;-dependent biomolecular oxidative damage; such properties are evident at therapeutically relevant drug concentrations, suggesting that UDCA could act as an antioxidant in vivo. 相似文献
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Rheumatoid factors (RF) were associated with alterations of antibody reactions to melanoma cells in vitro by two serologic assays. Removal of RF from melanoma patients' sera by absorption with Cohn's Fraction II coated latex particles enhanced seroreactivity in the Immune Adherence (IA) assay and diminished IgM detection by the Indirect Membrane Immunofluorescence (IMI) assay. The addition of serum with high titers of RF to these assay systems led to diminution of IA reactivity and enhancement of IgM detection by IMI. Since these factors are found in cancer patients' sera and can alter humoral immune reactions directed against antigens on the membranes of tumor cells, their presence should be recognized when performing assays with tumor target cells. RF may be of significance in the host-tumor relationship in vivo. 相似文献
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Francesca Di Giuliano Tommaso Perretta Francesca Pitocchi Noemi Pucci Maria Lina Serio Aurelia Caliandro Eliseo Picchi Valentina Ferrazzoli Chiara Adriana Pistolese Francesco Garaci Roberto Floris 《Radiology Case Reports》2022,17(7):2470
The presence of synchronous dual hematological diseases is an uncommon finding. We report an unusual case of coexistence of primary central nervous system lymphoma and primary breast lymphoma without systemic involvement in an immunocompetent patient. To our knowledge a similar case has not yet been reported in the literature. We especially focus on presenting the imaging features, the associated clinical findings and treatment management of each entity, with the aim of raising awareness on these two rare types of lymphomas and the possibility of their coexistence. 相似文献
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Caryn E. Peterson Rebecca L. Sedjo Faith G. Davis Craig A. Beam Anna R. Giuliano 《Nutrition and cancer》2013,65(6):728-733
Persistent infection with human papillomavirus (HPV) is the primary etiologic factor for cervical cancer. The synergistic effect of carotenoids on HPV persistence has not been examined. To explore these potential synergies, we developed 2 measures of carotenoid status using circulating and dietary intake nutrients in which each nutrient was given equal weighting. We then compared persistent HPV infection with its counterpart, intermittent infection. In the analysis using the Crude Index, no association was observed between circulating nutrients and persistent infection with oncogenic HPV [odds ratio (OR)adjusted = 0.8, 95% confidence interval (CI) = 0.3–2.2)] or any type HPV (ORadjusted = 0.8, 95% CI = 0.3–2.1). Similar results were obtained using the Cumulative Index. However, associations between dietary intake and persistent infection were observed using both indexes. When the analysis was restricted to oncogenic HPV, a 50% higher risk was observed for women with low dietary carotenoid status using the Crude Index (ORadjusted = 1.5, 95% CI = 0.6–3.7). In the analysis using any type HPV, the adjusted OR for women with low dietary intake of combined carotenoids using the Cumulative Index was 2.4 (95% CI = 1.1–5.2). These results may be consistent with the hypothesis that low levels of carotenoids may increase the risk of persistent HPV infection. 相似文献
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