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1.
D Gröne† R Treudler† EM de Villiers‡ R Husak† CE Orfanos† ChC Zouboulis†§ 《Journal of the European Academy of Dermatology and Venereology》2006,20(2):202-205
Cidofovir is an acyclic nucleoside phosphonate with broad-spectrum activity against DNA viruses, including human papilloma virus (HPV). However, data on the efficacy of cidofovir in an immunosuppressive setting remain contradictory. We report for the first time on the promotion of the healing of recalcitrant warts in a patient with myelodysplastic syndrome with intravenous cidofovir treatment. 相似文献
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L D Nord R C Willis T S Breen T L Avery R A Finch Y S Sanghvi G R Revankar R K Robins 《Biochemical pharmacology》1989,38(20):3543-3549
The basis for the antitumor activities of the exocyclic amino nucleosides 4-amino-(ARPP) and 4-methoxy-8-(D-ribofuranosylamino)pyrimido[5,4-d]pyrimidine (MRPP) was investigated. The primary target of these nucleosides appeared to be 5-phospho-alpha-D-ribofuranose-1-pyrophosphate (PRPP) synthetase. MRPP-5'-monophosphate was a competitive inhibitor (Ki = 40 microM) of the activation of this enzyme by the cofactor inorganic phosphate (K alpha = 2.2 mM). Consequently, ARPP and MRPP treatment of WI-L2 cultures rapidly inhibited both de novo pyrimidine and purine synthesis as well as the nucleotide salvage reactions dependent on PRPP, ARPP or MRPP treatment completely prevented [14C]bicarbonate incorporation into acid-soluble pyrimidine and purine nucleotides. The rate of salvage of [8-14C]hypoxanthine to form IMP was decreased by 85%. Treatment of cells with these agents caused a 50% reduction in the steady-state level of PRPP. When the capacity of the treated cells for sustained synthesis of PRPP was examined by adenine incorporation, the rate of adenine uptake was inhibited by greater than 50%. In vivo treatment of BDF1 mice with a single dose of ARPP (173 mg/kg) or MRPP (62 mg/kg) extended the mean life span of the mice, which had been inoculated intraperitoneally 1 day earlier with 1 x 10(6) L1210 murine leukemia cells, by 62 and 82% respectively. These studies indicate that MRPP and ARPP inhibit PRPP synthetase, and that PRPP synthetase may be a viable target in the development of certain antitumor agents. 相似文献
4.
Nonvoluntary sexual activity among adolescents 总被引:3,自引:0,他引:3
Data from the 1987 round of the National Survey of Children indicate that seven percent of Americans aged 18-22 have experienced at least one episode of nonvoluntary sexual intercourse. Women were more likely than men to report having had such an experience, with just under half of all nonvoluntary experiences among women occurring before the age of 14. Multiple classification analysis reveals that white women who had lived apart from their parents before age 16, those who had been brought up in poverty, those who had had a physical, emotional or mental limitation when they were young, those whose parents had been heavy drinkers, those whose parents had used illegal drugs and those whose parents had smoked cigarettes when they themselves were teenagers were at significantly greater risk for experiencing sexual abuse. Six percent of young white women with no risk factors, nine percent of those with one, 26 percent of those with two, and 68 percent of those with three or more had been sexually abused before or during adolescence. 相似文献
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The effect of three beta-lactamase inhibitors, clavulanic acid, sulbactam and tazobactam used in clinical practice were compared for their activity against purified beta-lactamases from Bacteroides uniformis, Clostridium butyricum and Fusobacterium nucleatum. The enzymes from B. uniformis and C. butyricum were produced in fermenters under controlled growth conditions and the enzyme from F. nucleatum was produced in batch cultures. Purification of the beta-lactamases was achieved by anion-exchange chromatography, gel filtration and FPLC-technique. The degree of inactivation of beta-lactamase activity was determined spectrophotometrically with nitrocefin as the substrate. The inhibitors in various concentrations were preincubated at 30 degrees C together with the enzyme for different time periods (0.5-120 min) before determination of the remaining beta-lactamase activity. The inhibitors all decreased the activity of the beta-lactamases investigated. Clavulanic acid and sulbactam were capable of reducing the enzyme activity of the B. uniformis beta-lactamase more effectively than the C. butyricum and F. nucleatum beta-lactamases. All beta-lactamases tested were more susceptible to tazobactam than to clavulanic acid and sulbactam. 相似文献
7.
Concentration and metabolic replacement (turnover) rate of glucose and ketone bodies were determined at intervals during a 52 day postweaning fast in five grey seal (Halichoerus grypus) pups, using bolus injections of radiotracers. Blood glucose was maintained at a high level throughout the fast, while beta-hydroxybutyrate increased 26 times from day 3 to day 37, whereafter it by and large was maintained. Glucose replacement rate decreased to 56% of the day 9 value at day 37 and dropped further to only 32% of the day 9 level at day 52 in two seals, while in another 2 seals it increased at this late stage. The average ketone body replacement rate ranged between 8.6 and 13.8 mumols min-1 kg-1, but did not change significantly (P greater than 0.05) during the fasting period. These results suggest a reduced gluconeogenesis from protein and increased production of ketone bodies, which may in part replace glucose as energy source during fasting. 相似文献
8.
Picotamide inhibition of excess in vitro thromboxane B2 release by colorectal mucosa in inflammatory bowel disease. 总被引:1,自引:0,他引:1
Collins CE Benson MJ Burnham WR Rampton DS 《Alimentary pharmacology & therapeutics》1996,10(3):315-320
BACKGROUND: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. METHODS: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. RESULTS: Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147- 325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61- 140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64- 206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM). CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease. 相似文献
9.
We examined the cross-sectional relationships between the frequency of habitual fish consumption, plasma phospholipid fatty acids, and serum lipids and lipoproteins in 152 men and women. There was a significant association between fish consumption starting from 1 dish/wk and plasma n-3, n-6, and n-9 fatty acids. Plasma eicosapentaenoic acid (EPA; 20: 5n-3) reflected fish consumption to a greater extent than did docosahexaenoic acid (DHA;22:6n-3). Triglycerides decreased (P less than 0.05) with fish consumption. In multivariate analysis in which anthropometric and lifestyle factors were controlled for, EPA correlated inversely with triglycerides (P less than 0.05) and positively with high-density-lipoprotein (HDL) cholesterol and apolipoprotein A-I (both P less than 0.001). In contrast, DHA did not correlate with triglycerides and showed negative associations to HDL cholesterol and apolipoprotein A-I (both P less than 0.001). Platelet phospholipid EPA, but not DHA, was associated with lower triglyceride and higher HDL-cholesterol concentrations (both P less than 0.05). This study suggests that long-term intake of small amounts of fish has biological effects, and that EPA and DHA have divergent relations with lipoprotein metabolism. 相似文献
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