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71.
Matthias Y. Kellermann Gunter Wegener Marcus Elvert Marcos Yukio Yoshinaga Yu-Shih Lin Thomas Holler Xavier Prieto Mollar Katrin Knittel Kai-Uwe Hinrichs 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(47):19321-19326
The methane-rich, hydrothermally heated sediments of the Guaymas Basin are inhabited by thermophilic microorganisms, including anaerobic methane-oxidizing archaea (mainly ANME-1) and sulfate-reducing bacteria (e.g., HotSeep-1 cluster). We studied the microbial carbon flow in ANME-1/ HotSeep-1 enrichments in stable-isotope–probing experiments with and without methane. The relative incorporation of 13C from either dissolved inorganic carbon or methane into lipids revealed that methane-oxidizing archaea assimilated primarily inorganic carbon. This assimilation is strongly accelerated in the presence of methane. Experiments with simultaneous amendments of both 13C-labeled dissolved inorganic carbon and deuterated water provided further insights into production rates of individual lipids derived from members of the methane-oxidizing community as well as their carbon sources used for lipid biosynthesis. In the presence of methane, all prominent lipids carried a dual isotopic signal indicative of their origin from primarily autotrophic microbes. In the absence of methane, archaeal lipid production ceased and bacterial lipid production dropped by 90%; the lipids produced by the residual fraction of the metabolically active bacterial community predominantly carried a heterotrophic signal. Collectively our results strongly suggest that the studied ANME-1 archaea oxidize methane but assimilate inorganic carbon and should thus be classified as methane-oxidizing chemoorganoautotrophs. 相似文献
72.
Satoshi Uchiyama Federica Andreoni Claudia Zürcher Katrin Schilcher Miriam Ender Jerzy Madon Ulrich Matt Partho Ghosh Victor Nizet Reto A. Schuepbach Annelies S. Zinkernagel 《Journal of molecular medicine (Berlin, Germany)》2013,91(7):861-869
Group A Streptococcus (GAS) is a human pathogen causing a wide range of mild to severe and life-threatening diseases. The GAS M1 protein is a major virulence factor promoting GAS invasiveness and resistance to host innate immune clearance. M1 displays an irregular coiled-coil structure, including the B-repeats that bind fibrinogen. Previously, we found that B-repeat stabilisation generates an idealised version of M1 (M1*) characterised by decreased fibrinogen binding in vitro. To extend these findings based on a soluble truncated version of M1, we now studied the importance of the B-repeat coiled-coil irregularities in full length M1 and M1* expressed in live GAS and tested whether the modulation of M1–fibrinogen interactions would open up novel therapeutic approaches. We found that altering either the M1 structure on the GAS cell surface or removing its target host protein fibrinogen blunted GAS virulence. GAS expressing M1* showed an impaired ability to adhere to and to invade human endothelial cells, was more readily killed by whole blood or neutrophils and most importantly was less virulent in a murine necrotising fasciitis model. M1-mediated virulence of wild-type GAS was strictly dependent on the presence and concentration of fibrinogen complementing our finding that M1–fibrinogen interactions are crucial for GAS virulence. Consistently blocking M1–fibrinogen interactions by fragment D reduced GAS virulence in vitro and in vivo. This supports our conclusion that M1–fibrinogen interactions are crucial for GAS virulence and that interference may open up novel complementary treatment options for GAS infections caused by the leading invasive GAS strain M1. 相似文献
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74.
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
75.
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78.
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79.
Helena Moratin Agmal Scherzad Thomas Gehrke Pascal Ickrath Katrin Radeloff Norbert Kleinsasser Stephan Hackenberg 《Environmental and molecular mutagenesis》2018,59(3):247-259
The increasing usage of zinc oxide nanoparticles (ZnO‐NPs) in industrial applications as well as in consumer products raises concern regarding their potential adverse effects to a greater extend. Numerous studies have demonstrated toxic properties of NPs, however there is still a lack of knowledge concerning the underlying mechanisms. This study was designed to systematically investigate cytotoxicity, apoptosis, cell cycle alterations, and genotoxicity induced by ZnO‐NP. Moreover, it was an aim of the investigations to specify the diverse effects of nanoparticle exposure in malignant in comparison with non‐malignant cells. Therefore, human head and neck squamous cell carcinoma‐derived FaDu cells were incubated with 4–20 µg/ml of ZnO‐NPs for 1–48 hr and tested for cell viability, cell cycle alterations, apoptosis and caspase‐3 gene expression as a sensitive marker of molecular apoptotic processes with regard to time‐ and dose‐dependent effects. Human mesenchymal bone marrow stem cells were used as non‐malignant representatives to examine oxidative stress‐related genotoxicity. Results showed a significant reduction in cell viability as well as dose‐ and time‐dependent increase of apoptotic cells following nanoparticle treatment. Likewise, caspase‐3 gene expression enhanced already before first apoptotic cells were detectable. It could be observed that doses that were cytotoxic in tumor cells did not reduce viability in stem cells. However, the same concentrations already induced significant DNA damage. The findings of the study suggest to keep a more critical eye on the use of nanoparticles as anti‐cancer agents. Yet, additional in vivo studies are needed to assess safety concerns for consumers and patients. Environ. Mol. Mutagen. 59:247–259, 2018. © 2017 Wiley Periodicals, Inc. 相似文献
80.
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