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971.
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Mose T Kjaerstad MB Mathiesen L Nielsen JB Edelfors S Knudsen LE 《Journal of toxicology and environmental health. Part A》2008,71(15):984-991
Ex vivo perfusion of the human term placenta is a method to study placental transfer without extrapolation from animal to human and with no ethical concerns for mother and child. However, ex vivo placenta perfusion has a limited potential within chemical screening and testing as the method is time-consuming. This study was an attempt to construct data needed to develop quantitative structure-activity relationship (QSAR) models that are able to predict placental transfer of new compounds. Placental transfer is a biological activity that statistically may be related to the physiochemical properties of a given group of compounds. Benzoic acid, caffeine, and glyphosate were chosen as model compounds because they are small molecules with large differences in physiochemical properties. Caffeine crossed the placenta by passive diffusion. The initial transfer rate of benzoic acid was more limited in the first part of the perfusion compared to caffeine, but reached the same steady-state level by the end of perfusion. The transfer of glyphosate was restricted throughout perfusion, with a lower permeation rate, and only around 15% glyphosate in maternal circulation crossed to the fetal circulation during the study period. 相似文献
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Gao QT Cheung JK Choi RC Cheung AW Li J Jiang ZY Duan R Zhao KJ Ding AW Dong TT Tsim KW 《Planta medica》2008,74(4):392-395
Danggui Buxue Tang (DBT), a Chinese medicinal decoction used commonly for treating women's ailments, contains Radix Astragali (RA) and Radix Angelicae Sinensis (RAS). According to Chinese medicinal theory, this decoction is to nourish the blood function; this, however, has not been demonstrated on the molecular level. In order to reveal the hematopoietic effect of this decoction, DBT was applied to cultured Hep3B human hepatocellular carcinoma cells. The treatment of DBT induced mRNA expression of erythropoietin (EPO) in a dose-dependent manner and peaked at approximately 2.5-fold induction. The secreted EPO in cultured Hep3B cells was quantified by ELISA: the treatment of DBT potentiated the effect of hypoxia-induced EPO expression in the cultured cells. In addition, the DBT-induced EPO expression could be abolished by pre-treatment with U0126, a mitogen-activated kinase inhibitor. The current results verified the hematopoietic function of this ancient herbal decoction. 相似文献
974.
Tina Panchal Sandra Baldwin Martin Østergaard Erik Soeren Halvard Hansen Vibeke Backer Morten Hostrup Peter Daley-Yates 《Drug testing and analysis》2023,15(5):495-505
A bioanalytical method for detecting the ultra-long-acting beta2-agonist (U-LABA) inhaled vilanterol and its metabolites, GSK932009 and GW630200, in urine was developed to potentially monitor permitted therapeutic versus prohibited supratherapeutic use in sport. The World Anti-Doping Agency (WADA) has established urinary concentration thresholds for the beta2-agonists salbutamol and formoterol. Therapeutic use of vilanterol (25 μg once daily) was recently permitted by WADA; however, there is no established decision limit for adverse analytical findings due to insufficient urine concentration data. In this study, we validated an assay to detect vilanterol in urine collected from four healthy male and female athletes 0–72 h who received inhaled corticosteroid fluticasone furoate/U-LABA vilanterol (800/100 μg) combination, four times the normal therapeutic dose. After administration, subjects performed 1 h of bike ergometer exercise. The experiment was conducted again after repeat dosing for 1 week. Our method utilised liquid chromatography with tandem mass spectrometry and was validated over urine concentrations of 5–5000 (vilanterol) and 50–50,000 pg/ml (GSK932009 and GW630200). Plasma samples were analysed for vilanterol, using a previously validated assay. The peak concentration values for urine vilanterol, GSK932009 and GW630200 were 9.5, 10.4 and 0.17 ng/ml, for single dosing, and 18.6, 19.5 and 0.20 ng/ml, for repeat dosing. Urine samples from four volunteers using the final validated method are reported, demonstrating this assay has sensitivity to detect vilanterol or GSK932009 in urine for ≥72 h post single or repeat dosing with 800/100 μg fluticasone furoate/vilanterol, whereas GW630200 was quantifiable ≤4 h post dose. 相似文献
975.
David Elmenhorst Tina Kroll Angela Oskamp Johannes Ermert Eva‐Maria Elmenhorst Franziska Wedekind Simone Beer Heinz H. Coenen Andreas Bauer 《Journal of sleep research》2016,25(6):754-761
The metabotrophic subtype 5 glutamate receptor (mGluR5) plays a critical role in synaptic plasticity besides its involvement in numerous neurological disorders, such as depression. As mGluR5 availability in humans is altered in sleep deprivation, we hypothesized that mGluR5 availability underlies a circadian variation. To investigate whether mGluR5 underlies potential circadian changes we measured its density in a randomized fashion at six different daytimes in 11 adult Sprague–Dawley rats. mGluR5 density was quantified by positron emission tomography (PET) using the radioactive ligand [11C]ABP688. [11C]ABP688 uptake was quantified in nine regions of interest with a reference tissue model. Significant differences in the binding potential (BPND) and therefore mGluR5 availability between the different circadian times were found in cortex, cingulate cortex, amygdala, caudate putamen and nucleus accumbens. Further post‐hoc statistical analysis (Tukey–Kramer test) of the different time‐points revealed significant changes in BPND between 07:00 hours (start of light‐on phase) and 15:00 hours (last time‐point of the light‐on phase) in the caudate putamen. This study shows that mGluR5 availability is increased during the light‐on, or sleep phase, of rodents by approximately 10%. Given that altered mGluR5 densities play a role in psychiatric disorders, further investigation is warranted to evaluate their circadian involvement in mood changes in humans. 相似文献
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Distinct iris gene expression profiles of primary angle closure glaucoma and primary open angle glaucoma and their interaction with ocular biometric parameters 下载免费PDF全文
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