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21.
Islet transplantation in type 1 diabetes: hype,hope and reality – a clinician's perspective 下载免费PDF全文
The β‐cell replacement by islet transplantation is an attractive approach for normalizing blood glucose without hypoglycaemia in patient with type 1 diabetes mellitus (T1D). A pioneer study by the Edmonton group more than a decade ago showed that alloislet transplantation may result in insulin independence for at least 1 year after transplantation. This breakthrough excited researchers, physicians and patients, who felt that the ultimate goal of cure for T1D was at hand. Longer follow‐up of patients who underwent islet transplantation showed less favourable results, with only approximately 10% of the patients remaining insulin‐free 5 years after transplantation. In the last few years, progress has been made, and the success rate of islet transplantation has steadily increased. Important hurdles, however, related to limited tissue supply and need for life‐long immunosuppressive drugs have yet to be overcome. Herein, we review recent achievements in islet transplantation and the challenges that still need to be addressed before this procedure can become a standard therapy for T1D. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
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Sramek JJ Leibowitz MT Weinstein SP Rowe ED Mendel CM Levy B McMahon FG Mullican WS Toth PD Cutler NR 《Journal of human hypertension》2002,16(1):13-19
Sibutramine is a serotonin-noradrenaline reuptake inhibitor that is effective for long-term weight reduction and maintenance in obese patients when used as an adjunct to dietary and behavioural measures. Because the inhibition of noradrenaline reuptake may be expected to increase systolic and diastolic blood pressure (SBP and DBP) and pulse rate (PR), a 12-week multi-centre, placebo-controlled, double-blind study was designed to evaluate the efficacy and tolerability of sibutramine for weight loss in obese patients whose hypertension was well controlled (DBP < or = 95 mm Hg) by beta-adrenergic blocking agents (beta-blockers), with or without concomitant thiazide diuretics. Of the 61 patients randomised to sibutramine 20 mg once daily or placebo, 55 patients (90%) completed the study. After 12 weeks, sibutramine-treated patients lost significantly more weight than placebo-treated patients: mean weight reductions were 4.2 kg (4.5%) in the sibutramine group vs 0.3 kg (0.4%) in the placebo group (P<0.001). Greater weight reduction on sibutramine was accompanied by trends for greater mean reductions in serum triglycerides and very low density lipoprotein cholesterol. Sibutramine was well tolerated, and most adverse events were mild or moderate in severity. No sibutramine patient discontinued treatment because of an adverse event. Mean supine and standing DBP and SBP were not statistically significantly different between the sibutramine group and the placebo group at any post-baseline visit during the 12-week trial. At week 12, mean increases from baseline supine SBP and DBP, respectively, were 1.6 and 1.7 mm Hg for the sibutramine group vs increases of 0.4 and 1.3 mm Hg for the placebo group. At week 12, mean increases from baseline standing SBP and DBP, respectively, were 1.5 and 1.8 mm Hg for the sibutramine group vs an increase of 0.3 and a decrease of 0.8 mm Hg for the placebo group (P > 0.05 for treatment comparison). A statistically significant mean increase of 5.6 bpm (+/-8.25, s.d.) in supine PR from a baseline of 62 bpm was reported in sibutramine-treated patients at week 12, whereas placebo-treated patients had a mean supine PR decrease of 2.2 bpm (+/-6.43) (P < 0.001). In summary, sibutramine was well tolerated and effective in weight reduction. The addition of sibutramine did not result in an increase in BP in obese patients whose hypertension was well controlled by a beta-blocker. However, based on the potential for changes in BP and PR, obese patients being treated with sibutramine should be monitored periodically for changes in BP and PR and managed appropriately. 相似文献
26.
A. Leibowitz Z. Faltin A. Perl Y. Eshdat Y. Hagay E. Peleg E. Grossman 《European journal of nutrition》2014,53(3):973-980
Purpose
Cumulative evidence suggests that moderate red wine consumption protects the cardiovascular system. The effect of cultured cells derived from red grape berry (RGC) on blood pressure (BP) has not been investigated. We therefore studied the antihypertensive effects of oral consumption of RGC in experimental rat model of metabolic-like syndrome and assessed its effect on human umbilical vein endothelial cells (HUVECs).Methods
Forty male Sprague–Dawley rats were fed for 5 weeks with either a high fructose diet (HFD) (n = 10) or HFD supplemented, during the last 2 weeks, with different doses (200, 400 and 800 mg/kg/day) of RGC suspended in their food (n = 30). BP, plasma triglycerides, insulin and adiponectin levels were measured at the beginning and after 3 and 5 weeks of diet. RGC effect on vasodilatation was evaluated by its ability to affect endothelin-1 (ET-1) production and endothelial nitric oxide synthase (eNOS) expression in HUVECs.Results
BP, plasma triglycerides, insulin and adiponectin increased significantly in rats fed with a HFD. The increase in BP, plasma triglycerides and insulin was attenuated by RGC supplementation. Incubation of HUVECs with RGC demonstrated a concentration-dependent inhibition of ET-1 secretion and increase in the level of eNOS, signaling a positive effect of RGC on vasodilatation.Conclusion
In rats with metabolic-like syndrome, RGC decreased BP and improved metabolic parameters. These beneficial effects may be mediated by the cell constituents, highly rich with polyphenols and resveratrol, reside in their natural state. 相似文献27.
David J. Whellan Pierluigi Tricoci Edmond Chen Zhen Huang David Leibowitz Pascal Vranckx Gregary D. Marhefka Claes Held Jose C. Nicolau Robert F. Storey Witold Ruzyllo Kurt Huber Peter Sinnaeve A. Teddy Weiss Jean-Pierre Dery David J. Moliterno Frans Van de Werf Philip E. Aylward Harvey D. White Paul W. Armstrong Lars Wallentin John Strony Robert A. Harrington Kenneth W. Mahaffey 《Journal of the American College of Cardiology》2014
28.
Ran D. Balicer Chandra J. Cohen Morton Leibowitz Becca S. Feldman Ilan Brufman Craig Roberts Moshe Hoshen 《Vaccine》2014
Background
Current pneumococcal vaccine campaigns take a broad, primarily age-based approach to immunization targeting, overlooking many clinical and administrative considerations necessary in disease prevention and resource planning for specific patient populations. We aim to demonstrate the utility of a population-specific predictive model for hospital-treated pneumonia to direct effective vaccine targeting.Methods
Data was extracted for 1,053,435 members of an Israeli HMO, age 50 and older, during the study period 2008–2010. We developed and validated a logistic regression model to predict hospital-treated pneumonia using training and test samples, including a set of standard and population-specific risk factors. The model's predictive value was tested for prospectively identifying cases of pneumonia and invasive pneumococcal disease (IPD), and was compared to the existing international paradigm for patient immunization targeting.Results
In a multivariate regression, age, co-morbidity burden and previous pneumonia events were most strongly positively associated with hospital-treated pneumonia. The model predicting hospital-treated pneumonia yielded a c-statistic of 0.80. Utilizing the predictive model, the top 17% highest-risk within the study validation population were targeted to detect 54% of those members who were subsequently treated for hospitalized pneumonia in the follow up period. The high-risk population identified through this model included 46% of the follow-up year's IPD cases, and 27% of community-treated pneumonia cases. These outcomes were compared with international guidelines for risk for pneumococcal diseases that accurately identified only 35% of hospitalized pneumonia, 41% of IPD cases and 21% of community-treated pneumonia.Conclusions
We demonstrate that a customized model for vaccine targeting performs better than international guidelines, and therefore, risk modeling may allow for more precise vaccine targeting and resource allocation than current national and international guidelines. Health care managers and policy-makers may consider the strategic potential of utilizing clinical and administrative databases for creating population-specific risk prediction models to inform vaccination campaigns. 相似文献29.
30.
M. Shaked M. Ketzinel-Gilad Y. Ariav E. Cerasi N. Kaiser G. Leibowitz 《Diabetologia》2009,52(4):636-644
Aims/hypothesis In type 2 diabetes, glucose toxicity leads to beta cell apoptosis with decreased beta cell mass as a consequence. Thioredoxin-interacting
protein (TXNIP) is a critical mediator of glucose-induced beta cell apoptosis. Since hyperglycaemia leads to elevated serum
insulin, we hypothesised that insulin is involved in the regulation of TXNIP protein levels in beta cells.
Methods We studied the production of TXNIP in INS-1E beta cells and in islets of Psammomys obesus, an animal model of type 2 diabetes, in response to glucose and different modulators of insulin secretion.
Results TXNIP production was markedly augmented in islets from diabetic P. obesus and in beta cells exposed to high glucose concentration. In contrast, adding insulin to the culture medium or stimulating
insulin secretion with different secretagogues suppressed TXNIP. Inhibition of glucose and fatty acid-stimulated insulin secretion
with diazoxide increased TXNIP production in beta cells. Nitric oxide (NO), a repressor of TXNIP, enhanced insulin signal
transduction, whereas inhibition of NO synthase abolished its activation, suggesting that TXNIP inhibition by NO is mediated
by stimulation of insulin signalling. Treatment of beta cells chronically exposed to high glucose with insulin reduced beta
cell apoptosis. Txnip knockdown mimicking the effect of insulin prevented glucose-induced beta cell apoptosis.
Conclusions/interpretation Insulin is a potent repressor of TXNIP, operating a negative feedback loop that restrains the stimulation of TXNIP by chronic
hyperglycaemia. Repression of TXNIP by insulin is probably an important compensatory mechanism protecting beta cells from
oxidative damage and apoptosis in type 2 diabetes.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users. 相似文献