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Marika A. Artz Johannes M. M. Boots Gerry Ligtenberg Joke I. Roodnat Maarten H. L. Christiaans Pieter F. Vos Philip Moons George Borm Luuk B. Hilbrands 《American journal of transplantation》2004,4(6):937-945
Long-term use of cyclosporine after renal transplantation results in nephrotoxicity and an increased cardiovascular risk profile. Tacrolimus may be more favorable in this respect. In this randomized controlled study in 124 renal transplant patients, the effects of conversion from cyclosporine to tacrolimus on renal function, cardiovascular risk factors, and perceived side-effects were investigated after a follow-up of 2 years. After conversion from cyclosporine to tacrolimus renal function remained stable, whereas continuation of cyclosporine was accompanied by a rise in serum creatinine from 142 +/- 48 micromol/L to 157 +/- 62 micromol/L (p < 0.05 comparing both groups). Conversion to tacrolimus resulted in a sustained reduction in systolic and diastolic blood pressure, and a sustained improvement in the serum lipid profile, leading to a reduction in the Framingham risk score from 5.7 +/- 4.3 to 4.8 +/- 5.3 (p < 0.05). Finally, conversion to tacrolimus resulted in decreased scores for occurrence of and distress due to side-effects. In conclusion, conversion from cyclosporine to tacrolimus in stable renal transplant patients is beneficial with respect to renal function, cardiovascular risk profile, and side-effects. Therefore, for most renal transplant patients tacrolimus will be the drug of choice when long-term treatment with a calcineurin inhibitor is indicated. 相似文献
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Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS 总被引:18,自引:0,他引:18
Storkebaum E Lambrechts D Dewerchin M Moreno-Murciano MP Appelmans S Oh H Van Damme P Rutten B Man WY De Mol M Wyns S Manka D Vermeulen K Van Den Bosch L Mertens N Schmitz C Robberecht W Conway EM Collen D Moons L Carmeliet P 《Nature neuroscience》2005,8(1):85-92
Neurotrophin treatment has so far failed to prolong the survival of individuals affected with amyotrophic lateral sclerosis (ALS), an incurable motoneuron degenerative disorder. Here we show that intracerebroventricular (i.c.v.) delivery of recombinant vascular endothelial growth factor (Vegf) in a SOD1(G93A) rat model of ALS delays onset of paralysis by 17 d, improves motor performance and prolongs survival by 22 d, representing the largest effects in animal models of ALS achieved by protein delivery. By protecting cervical motoneurons, i.c.v. delivery of Vegf is particularly effective in rats with the most severe form of ALS with forelimb onset. Vegf has direct neuroprotective effects on motoneurons in vivo, because neuronal expression of a transgene expressing the Vegf receptor prolongs the survival of SOD1(G93A) mice. On i.c.v. delivery, Vegf is anterogradely transported and preserves neuromuscular junctions in SOD1(G93A) rats. Our findings in preclinical rodent models of ALS may have implications for treatment of neurodegenerative disease in general. 相似文献
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Disruption of the plasminogen gene in mice abolishes wound healing after myocardial infarction 总被引:12,自引:0,他引:12 下载免费PDF全文
Creemers E Cleutjens J Smits J Heymans S Moons L Collen D Daemen M Carmeliet P 《The American journal of pathology》2000,156(6):1865-1873
The plasminogen system plays an important role in the proteolytic degradation of extracellular matrices during wound healing. In the present study we investigated the impact of the plasminogen system on cardiac wound healing and function after myocardial infarction. Myocardial infarction was induced in plasminogen-deficient mice (Plg-/-) and in wild-type controls (Plg+/+). Structural analysis 1, 2, and 5 weeks after infarction revealed that infarct healing was virtually abolished in Plg-/- mice, indicating that the plasminogen system is required for the repair process of the heart after infarction. In the absence of plasminogen, inflammatory cells did not migrate into the infarcted myocardium. Necrotic cardiomyocytes were not removed and the formation of granulation tissue and fibrous tissue did not occur. In these non-healing infarcted hearts, LV dilatation was not altered. In addition, gelatinolytic activity of MMP-2 and MMP-9 was depressed in the Plg-/- infarcted hearts, suggesting that the plasmin effect on infarct healing may be mediated by MMPs. Surprisingly, cardiac function was only attenuated to a rather small extent in the Plg-/- infarcted mice when compared to the wild-types. This study provides direct prove that plasmin-mediated proteolysis plays a central role in cardiac wound healing after myocardial infarction in mice. 相似文献
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In the action of thrombocytes during stemming of a bleeding after damage to a blood vessel, receptors on the thrombocyte membrane play an important part. Adhesion of platelets takes place via specific binding of receptors; the main binding is that of glycoprotein (Gp) Ib to Von Willebrand factor which is synthetized by endothelial cells. Activation of thrombocytes is stimulated by adhesion and by agonists. Weak agonists, through production of thromboxane A2 and release of agonists from granules cause a self-fortifying process of thrombocyte stimulation; strong agonists (like thrombin) lead also to activation of Gp IIb/IIIa receptors. Aggregation of thrombocytes occurs after activation of Gp IIb/IIIa receptors. During stimulation, a change of shape occurs which enables binding to suitable plasma proteins of which the main one is fibrinogen. Knowledge of thrombocyte receptors enhances the insight into the prognosis and efficacy of certain treatments in diseases in which platelet aggregation is pivotal. Of the six categories of antiplatelet drugs, antagonists of Gp IIb/IIIa receptors are the most potent. In clinical trials good results have been obtained in patients with coronary disease of the intravenously administered form added to acetylsalicylic acid. 相似文献
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van Klei WA Moons KG Rutten CL Knape JT Grobbee DE 《Nederlands tijdschrift voor geneeskunde》2000,144(29):1389-1393
The report of the Netherlands Health Council 'Preoperatief onderzoek; een herijking van uitgangspunten' recommends that the health status of patients aged 16-39 years can be investigated preoperatively by the anaesthesiologist using a short questionnaire (6 questions). However, it is not clear whether such an abbreviated preoperative investigation will be informative enough for a safe and balanced anaesthesiologic management. An overview of relevant literature on the subject of preoperative investigation indicates that the preoperative physical status of patients as reflected by the American Society of Anesthesiologists (ASA) classification is a predictor of perioperative complications. Patients can be classified accordingly on the basis of an extended history and physical examination only: any routine additional investigation, such as ECG, chest X-ray or laboratory investigations, seem superfluous. Only blood group, rhesus factor and the presence of irregular antibodies may need to be determined if indicated by the kind of surgery. Currently, however, there is not sufficient evidence to demonstrate that the short questionnaire of the Netherlands Health Council is informative enough. 相似文献
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C Matthys M Bilau Y Govaert E Moons S De Henauw J L Willems 《Food and chemical toxicology》2005,43(2):271-278
Acrylamide has recently been found in a range of heat treated food items. As it is a neurotoxic agent and a probable, human carcinogen (IARC 2A), human exposure to this chemical might constitute an important public health issue. The purpose of the study was to estimate the acrylamide intake in Flemish adolescents (based on 7-day food record) and to evaluate the possible health risks due to the exposure. The Belgian Federal Agency for the Safety of the Food Chain collected 150 food items from different supermarkets and restaurants to analyse the acrylamide level. The limit of quantitation was 30 microg acrylamide/kg foodstuffs. Exposure modelling was based on Monte Carlo simulations. The estimated dietary intake of acrylamide per person given as the 5th, 50th and 95th percentile were 0.19, 0.51 and 1.09 mircog/kg bw/d. Bread, despite its low acrylamide content, is relevant as a source of acrylamide exposure at the lower percentiles. At higher percentiles the contribution of French fries and crisps is more important. It must be emphasised that the exposure assessment has several limitations. Risk of neurotoxicity seems negligible. The relevance of current intake levels in terms of cancer risk remains a subject of debate. 相似文献
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Joline W.J. Beulens Yvonne T. van der Schouw Karel G.M. Moons Hendriek C. Boshuizen Daphne L. van der A Rolf H.H. Groenwold 《Annals of epidemiology》2013,23(4):193-197
PurposeModerate alcohol consumption is associated with a reduced type 2 diabetes risk, but the biomarkers that explain this relation are unknown. The most commonly used method to estimate the proportion explained by a biomarker is the difference method. However, influence of alcohol–biomarker interaction on its results is unclear. G-estimation method is proposed to accurately assess proportion explained, but how this method compares with the difference method is unknown.MethodsIn a case–cohort study of 2498 controls and 919 incident diabetes cases, we estimated the proportion explained by different biomarkers on the relation between alcohol consumption and diabetes using the difference method and sequential G-estimation method.ResultsUsing the difference method, high-density lipoprotein cholesterol explained the relation between alcohol and diabetes by 78% (95% confidence interval [CI], 41–243), whereas high-sensitivity C-reactive protein (?7.5%; ?36.4 to 1.8) or blood pressure (?6.9; ?26.3 to ?0.6) did not explain the relation. Interaction between alcohol and liver enzymes led to bias in proportion explained with different outcomes for different levels of liver enzymes. G-estimation method showed comparable results, but proportions explained were lower.ConclusionsThe relation between alcohol consumption and diabetes may be largely explained by increased high-density lipoprotein cholesterol but not by other biomarkers. Ignoring exposure–mediator interactions may result in bias. The difference and G-estimation methods provide similar results. 相似文献