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61.
Magnus Edner Vernon V. S. Bonarjee Dennis W. T. Nilsen Jens Berning Steen Carstensen Kenneth Caidahl 《Clinical cardiology》1996,19(7):543-548
Background and hypothesis: Although the angiotensin-converting enzyme inhibitor enalapril has recently been shown to reduce mortality and the need for hospitalization in patients with left ventricular dysfunction and congestive heart failure, this drug was found to have no significant impact on short-term mortality after acute myocardial infarction (AMI) in the CONSENSUS II trial. The effect of enalapril initiated early after AMI on clinical and echocardiographic determinants of left ventricular (LV) function was studied in a subset of patients from CONSENSUS II Methods: Symptoms and signs of heart failure were classified as NYHA and dyspnea classes. Echocardiography included LV end-systolic volumes (ESV) and end-diastolic volumes (EDV), as well as ejection fraction (EF). wall motion index (WMI), and mitral flow indices. In all, 428 patients were included and followed for an average of 5.1 months by serial examinations, starting 2–5 days after myocardial infarction (MI) and repeated after 1 month and at the completion of the study. Results: There was no beneficial effect of enalapril on clinically determined function. Changes (i.e. changes in NYHA class) in the functional status remained correlated with changes in echocardiographic determinants throughout the study in patients belonging to the placebo group: EDV index (r=0.36, p = 0.002, ESV index (r = 0.49, p < 0.001), EF (r = -0.41, p < 0.001), and WMI (r=0.29, p = 0.008). In a stepwise logistic regression model, the best baseline parameters to predict NYHA class at final visit in all patients were age (p = 0.014) and ESV index (p = 0.001). Conclusion: Enalapril treatment for an average period of 5.1 months following MI resulted in no clinically significant beneficial effects on NYHA and dyspnea class. Changes in clinical function class were correlated with changes in echocardiographic determinants in placebo-treated patients, but not in patients given enalapril. 相似文献
62.
Guinea pig embryo (GEP) cells were transformed in vitro by the Kirsten strain of mouse sarcoma virus (Ki-MSV). The transformed cells were found to release infectious virus continuously and produced high titers of group-specific (gs) complement-fixing (CF) antigen characteristics of the murine sarcoma-leukemia virus complex. Foci of transformed cells were similar in appearance to those obtained with Ki-MSV in mouse and rat cells. The transformed cells produced RNA dependent DNA polymerase and type C virus particles with a density of approximately 1.15 g/ml in sucrose gradients by 3H-uridine labeling. The transformed cells produced tumors when transplanted into newborn guinea pigs. A number of focus-derived clonal lines from Ki-MSV transformed cells were isolated and characterized. All the focus-derived lines were found to be either producers or nonproducers (NP). The NP guinea pig cells produced neither infectious virus nor viral antigens of the murine sarcoma-leukemia virus complex although they were morphologically indistinguishable from virus-releasing MSV transformed GPE lines and produced tumors when transplanted into newborn guinea pigs. However, the sarcoma virus genome could be rescued in these NP cells by cocultivation with "helper" murine leukemia virus (MuLV) releasing GPE cells. Particles resembling guinea pig leukemia virus were activated from guinea pig NP cells or cultured normal guinea pig cells following chemical treatment. These particles were approximately 100 nm in the mature form and had a density of 1.16-1.17 g/ml. They contained RNA dependent DNA polymerase activity. 相似文献
63.
Mitchell Gersovitz Hamish N. Munro John Udall Vernon R. Young 《Metabolism: clinical and experimental》1980,29(11):1075-1086
Albumin synthesis was evaluated in 5 young adult males (19–25 yr) and 6 elderly males (64–78 yr) by a procedure involving oral administration of 15N-glycine every 3 hr over a 60-hr period. From about 40 hr onwards, urinary urea achieved a plateau of 15N-enrichment, which was estimated from the average of the last five (low protein) or seven (adequate protein) consecutive three-hourly urinary samples of the 60-hr period. This enrichment plateau was used as an index of the 15N-enrichment of the guanidine N of hepatic free arginine. The 15N-enrichment of the guanidine N of arginine in serum albumin was determined and albumin synthesis was estimated by comparing this value with the estimated enrichment of precursor hepatic arginine. Using this methodology, serum albumin concentration, synthesis, rate and plasma volume were measured when the young and elderly subjects had received an adequate protein intake (1.5 g · kg?1 for 7 days) or a low protein intake (0.4 g · kg?1 for 14 days). Serum albumin concentration was lower in the elderly at both levels of protein intake; protein intake did not affect this parameter in either age-group. Plasma volume (per kg body weight) did not differ between young and old, but increased in both groups when they were given the low-protein diet, so that the total intravascular albumin mass increased in both age groups significantly in the case of the young, and was probably due to net transfer of albumin from the extravascular pool. The fractional synthesis rate of the whole body albumin pool with adequate intake of protein was 4.0%/day in the young and 3.4%/day in the elderly. This fractional rate was reduced significantly by giving the low-protein diet to the young subjects, but was not reduced in the elderly. Absolute synthesis rates, calculated per kg body weight and per kg body cell mass, led to a similar conclusion. Whole body protein synthesis was also estimated from urinary 15N-urea enrichment using the Picou and Taylor-Roberts model. Albumin synthesis as a percentage of whole body protein synthesis (5%–6%) was reduced in the young adults by giving the low-protein diet, but was unchanged in the elderly. In conclusion, the rate of albumin synthesis in the young, but not in the elderly, is sensitive to changes in protein intake. It is suggested that albumin synthesis in the elderly is controlled at a lower set point, which prevents its response to higher protein intakes. 相似文献
64.
65.
Breen DM Dolinsky VW Zhang H Ghanim H Guo J Mroziewicz M Tsiani EL Bendeck MP Dandona P Dyck JR Heximer SP Giacca A 《Atherosclerosis》2012,222(2):375-381
Revascularization procedures used for treatment of atherosclerosis often result in restenosis. Resveratrol (RSV), an antioxidant with cardiovascular benefits, decreases neointimal formation after arterial injury by a mechanism that is still not fully clarified. Our main objective was to address the role of nitric oxide synthases (NOSes) and more specifically the endothelial-NOS (eNOS) isoform as a mediator of this effect. RSV (4 mg/kg/day, s.c.) alone or in combination with the NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME) (2 mg/kg/day, s.c.) was given to Sprague-Dawley rats beginning at 3 days before arterial (carotid or aortic) injury. RSV reduced neointimal formation by 50% (P<0.01), decreased intimal cell proliferation by 37% (P<0.01) and reduced inflammatory markers such as PECAM and MMP-9 mRNA. These effects of RSV were all abolished by coadministration of l-NAME. Oral RSV (beginning at 5 days before arterial injury) reduced neointimal thickness after femoral wire injury in mice, however this effect was not observed in eNOS knockout mice. This is the first report of RSV decreasing neointimal cell proliferation and neointimal growth through an eNOS-dependent mechanism. 相似文献
66.
Dickhaut J Lin S Porter D Smith V 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(5):1425-1430
The original double auction studies of supply and demand markets established their strong efficiency and equilibrium convergence behavior using economically unsophisticated and untrained subjects. The results were unexpected because all individual costs and values were private and dependent entirely on the market trading process to aggregate the dispersed information into socially desirable outcomes. The exchange environment, however, corresponded to that of perishable, and not re-traded goods in which participants were specialized as buyers or sellers. We report experiments in repeated single-period markets where tradability, and buyer-seller role specialization, is varied by imposing or relaxing a restriction on re-trade within each period. In re-trade markets scope is given to speculative motives unavailable where goods perish on purchase. We observe greatly increased trade volume and decreased efficiency but subject experience increases efficiency. Observed speculation slows convergence by impeding the process whereby individuals learn from the market whether their private circumstances lead them to specialize as buyers or sellers. 相似文献
67.
VL Scarborough NP Dunning KB Tankersley C Carr E Weaver L Grazioso B Lane JG Jones P Buttles F Valdez DL Lentz 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(31):12408-12413
The access to water and the engineered landscapes accommodating its collection and allocation are pivotal issues for assessing sustainability. Recent mapping, sediment coring, and formal excavation at Tikal, Guatemala, have markedly expanded our understanding of ancient Maya water and land use. Among the landscape and engineering feats identified are the largest ancient dam identified in the Maya area of Central America; the posited manner by which reservoir waters were released; construction of a cofferdam for dredging the largest reservoir at Tikal; the presence of ancient springs linked to the initial colonization of Tikal; the use of sand filtration to cleanse water entering reservoirs; a switching station that facilitated seasonal filling and release; and the deepest rock-cut canal segment in the Maya Lowlands. These engineering achievements were integrated into a system that sustained the urban complex through deep time, and they have implications for sustainable construction and use of water management systems in tropical forest settings worldwide. 相似文献
68.
69.
Pellicoro A Aucott RL Ramachandran P Robson AJ Fallowfield JA Snowdon VK Hartland SN Vernon M Duffield JS Benyon RC Forbes SJ Iredale JP 《Hepatology (Baltimore, Md.)》2012,55(6):1965-1975
Elastin has been linked to maturity of liver fibrosis. To date, the regulation of elastin secretion and its degradation in liver fibrosis has not been characterized. The aim of this work was to define elastin accumulation and the role of the paradigm elastase macrophage metalloelastase (MMP-12) in its turnover during fibrosis. Liver fibrosis was induced by either intraperitoneal injections of carbon tetrachloride (CCl(4) ) for up to 12 weeks (rat and mouse) or oral administration of thioacetamide (TAA) for 1 year (mouse). Elastin synthesis, deposition, and degradation were investigated by immunohistochemistry, quantitative polymerase chain reaction (qPCR), western blotting, and casein zymography. The regulation of MMP-12 elastin degradation was defined mechanistically using CD11b-DTR and MMP-12 knockout mice. In a CCl(4) model of fibrosis in rat, elastin deposition was significantly increased only in advanced fibrosis. Tropoelastin expression increased with duration of injury. MMP-12 protein levels were only modestly changed and in coimmunoprecipitation experiments MMP-12 was bound in greater quantities to its inhibitor TIMP-1 in advanced versus early fibrosis. Immunohistochemistry and macrophage depletion experiments indicated that macrophages were the sole source of MMP-12. Exposure of CCl(4) in MMP-12(-/-) mice led to a similar degree of overall fibrosis compared to wildtype (WT) but increased perisinusoidal elastin. Conversely, oral administration of TAA caused both higher elastin accumulation and higher fibrosis in MMP-12(-/-) mice compared with WT. Conclusion: Elastin is regulated at the level of degradation during liver fibrosis. Macrophage-derived MMP-12 regulates elastin degradation even in progressive experimental liver fibrosis. These observations have important implications for the design of antifibrotic therapies. 相似文献
70.
LaRocque RC Rao SR Lee J Ansdell V Yates JA Schwartz BS Knouse M Cahill J Hagmann S Vinetz J Connor BA Goad JA Oladele A Alvarez S Stauffer W Walker P Kozarsky P Franco-Paredes C Dismukes R Rosen J Hynes NA Jacquerioz F McLellan S Hale D Sofarelli T Schoenfeld D Marano N Brunette G Jentes ES Yanni E Sotir MJ Ryan ET;Global TravEpiNet Consortium 《Clinical infectious diseases》2012,54(4):455-462