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71.
Isabel Meister Katrin Ingram-Sieber Noemi Cowan Matthew Todd Murray N. Robertson Claudia Meli Malay Patra Gilles Gasser Jennifer Keiser 《Antimicrobial agents and chemotherapy》2014,58(9):5466-5472
A racemic mixture of R and S enantiomers of praziquantel (PZQ) is currently the treatment of choice for schistosomiasis. Though the S enantiomer and the metabolites are presumed to contribute only a little to the activity of the drug, in-depth side-by-side studies are lacking. The aim of this study was to investigate the in vitro activities of PZQ and its main metabolites, namely, R- and S-cis- and R- and S-trans-4′-hydroxypraziquantel, against adult worms and newly transformed schistosomula (NTS). Additionally, we explored the in vivo activity and hepatic shift (i.e., the migration of the worms to the liver) produced by each PZQ enantiomer in mice. Fifty percent inhibitory concentrations of R-PZQ, S-PZQ, and R-trans- and R-cis-4′-hydroxypraziquantel of 0.02, 5.85, 4.08, and 2.42 μg/ml, respectively, for adult S. mansoni were determined in vitro. S-trans- and S-cis-4′-hydroxypraziquantel were not active at 100 μg/ml. These results are consistent with microcalorimetry data and studies with NTS. In vivo, single 400-mg/kg oral doses of R-PZQ and S-PZQ achieved worm burden reductions of 100 and 19%, respectively. Moreover, worms treated in vivo with S-PZQ displayed an only transient hepatic shift and returned to the mesenteric veins within 24 h. Our data confirm that R-PZQ is the main effector molecule, while S-PZQ and the metabolites do not play a significant role in the antischistosomal properties of PZQ. 相似文献
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Claudia Schulz Gisela Büchele Martin Rehm Dietrich Rothenbacher Patrick Roigk Kilian Rapp Christian Günster Hans-Helmut König Katrin Reber 《Journal of the American Medical Directors Association》2019,20(4):451-455.e3
Objectives
Hip fractures are common consequences of falls in older adults and, among other negative health outcomes, often lead to care dependence in the long term. Until 2016, the German long-term care insurance classified care recipients according to a standardized classification system consisting of 3 care levels. It was based on required assistance in performing activities of daily living and assessed by a qualified physician or nurse. Thus, care level reflects the degree of care dependence. The aim of this study was to determine relevant patient characteristics, which are related to the likelihood of increasing care dependence in terms of worsening care level after hip fracture.Design
Retrospective cohort study.Setting and participants
Statutory health insurance claims data including 122,922 insured individuals living in Germany and aged 65 years or older, who sustained a hip fracture from 2009 through 2011.Measures
The association of patient characteristics with worsening care level in the quarterly period after hip fracture was investigated by means of multinomial logit regression analysis. Death constitutes a competing risk and was modeled as additional nominal outcome.Results
Among all patients, crude rates were 30.9% for worsening care level, 54.8% for unchanged care level, and 14.4% for death after hip fracture. The multivariate analysis revealed that patient factors male sex, increasing age, increasing comorbidity, increasing inpatient length of stay, and a lack of inpatient rehabilitation were significantly associated with a worsening care level.Conclusions/Implications
This study uses the German standardized measurement of care dependence in terms of worsening care level after hip fracture and finds various related patient characteristics. Knowledge of these characteristics helps to identify possible risk groups for care dependence after hip fracture, for which special attention can be provided regarding treatment and prevention of hip fractures. 相似文献75.
Katrin Sak 《Nutrition and cancer》2017,69(8):1119-1150
Several epidemiological findings have demonstrated that specific flavonoids can be responsible for reduction of the risk of certain cancer types. However, these results are still rather limited, inconclusive and controversial. Therefore, in this comprehensive review article the findings reported to date about the associations between dietary intake of individual flavonoid compounds and cancer incidence are compiled and analyzed. Also, the possible reasons for inconsistencies are brought forth and discussed. As diet is a potentially modifiable factor in our behavioral choices, further large-scale prospective studies with longer follow-up times, different populations, various doses and exposure timing as well as diverse well-controlled confounders are highly needed to confirm or disprove the current epidemiological knowledge about the role of flavonoids on cancer risk. Regarding the promising data to date, more research on bioavailability, metabolism and biological action mechanisms of these plant secondary metabolites is also encouraged. 相似文献
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Jan Kottner Janet Cuddigan Keryln Carville Katrin Balzer Dan Berlowitz Susan Law Mary Litchford Pamela Mitchell Zena Moore Joyce Pittman Dominique Sigaudo-Roussel Chang Yee Yee Emily Haesler 《Journal of tissue viability》2019,28(2):51-58
Aim
The European Pressure Ulcer Advisory Panel, the Pan Pacific Pressure Injury Alliance, and the National Pressure Ulcer Advisory Panel are updating the ‘Prevention and Treatment of Pressure Ulcers: Clinical Practice Guideline’ (CPG) in 2019. The aim of this contribution is to summarize and to discuss the guideline development protocol for the 2019 update.Methods
A guideline governance group determines and monitors all steps of the CPG development. An international survey of consumers will be undertaken to establish consumer needs and interests. Systematic evidence searches in relevant electronic databases cover the period from July 2013 through August 2018. Risk of bias of included studies will be assessed by two reviewers using established checklists and an overall strength of evidence assigned to the cumulative body of evidence. Small working groups review the evidence available for each topic, review and/or draft the guideline chapters and recommendations and/or good practice statements. Finally, strength of recommendation grades are assigned. The recommendations are rated based on their importance and their potential to improve individual patient outcomes using an international formal consensus process.Discussion
Major methodological advantages of the current revision are a clear distinction between evidence-based recommendations and good practice statements and strong consumer involvement.Conclusion
The 2019 guideline update builds on the previous 2014 version to ensure consistency and comparability. Methodology changes will improve the guideline quality to increase clarity and to enhance implementation and compliance. The full guideline development protocol can be accessed from the guideline website (http://www.internationalguideline.com/). 相似文献77.
Melatonin promotes sorafenib‐induced apoptosis through synergistic activation of JNK/c‐jun pathway in human hepatocellular carcinoma 下载免费PDF全文
Shibo Lin Katrin Hoffmann Chao Gao Marius Petrulionis Ingrid Herr Peter Schemmer 《Journal of pineal research》2017,62(3)
Melatonin has been shown to exert anticancer activity on hepatocellular carcinoma (HCC) through its antiproliferative and pro‐apoptotic effect in both experimental and clinical studies, and sorafenib is the only approved drug for the systemic treatment of HCC. Thus, this study was designed to investigate the combined effect of melatonin and sorafenib on proliferation, apoptosis, and its possible mechanism in human HCC. Here, we found that both melatonin and sorafenib resulted in a dose‐dependent growth inhibition of HuH‐7 cells after 48 hours treatment, and the combination of them enhanced the growth inhibition in a synergistic manner. Colony formation assay indicated that co‐treatment of HuH‐7 cells with melatonin and sorafenib significantly decreased the clonogenicity compared to the treatment with single agent. Furthermore, FACS and TUNEL assay confirmed that melatonin synergistically augmented the sorafenib‐induced apoptosis after 48 hours incubation, which was in accordance with the activation of caspase‐3 and the JNK/c‐jun pathway. Inhibition of JNK/c‐jun pathway with its inhibitor SP600125 reversed the phosphorylation of c‐jun and the activation of caspase‐3 induced by co‐treatment of HuH‐7 cells with melatonin and sorafenib in a dose‐dependent manner. Furthermore, SP600125 exhibited protective effect against apoptosis induced by the combination of melatonin and sorafenib. This study demonstrates that melatonin in combination with sorafenib synergistically inhibits proliferation and induces apoptosis in human HCC cells; therefore, supplementation of sorafenib with melatonin may serve as a potential therapeutic choice for advanced HCC. 相似文献
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