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排序方式: 共有707条查询结果,搜索用时 15 毫秒
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Sinisa Stojkovic MD PhD Miodrag Ostojic MD PhD Milan Nedeljkovic MD PhD Goran Stankovic MD PhD Branko Beleslin MD PhD Vladan Vukcevic MD Dejan Orlic MD Aleksandra Arandjelovic MD PhD Jelena Kostic MD Miodrag Dikic MD Miloje Tomasevic MD PhD 《Catheterization and cardiovascular interventions》2010,75(3):317-325
Objectives : The aim of this study was to assess the role of short oral administration of rapamycin, without loading dose, in the reduction of restenosis rate after bare metal stent implantation. Background : Previous studies suggest that the administration of oral rapamycin reduces angiographic restenosis after bare metal stent implantation. Methods : This was prospective, open‐label study of 80 patients randomized to either oral rapamycin (2 mg/day for 30 days, starting within 24 hr of stent implantation) or no therapy after implantation of a coronary bare metal stent. The primary study end point was incidence of angiographic binary restenosis and late loss at six months. The secondary end points were target lesion revascularization (TLR), target vessel revascularization (TVR), and incidence of major adverse cardiovascular events (MACE) at 6 months. Results : Angiographic follow up was completed in 72/80 (90%) of patients. In the rapamycin group, the drug was well tolerated (22.5% minor side effects) and was maintained in 100% of patients. At six months, the in‐segment binary restenosis was 10.5% in rapamycin group vs. 51.4% in no‐therapy group, P < 0.001) and the in‐stent binary restenosis was 7.9% in rapamycin group vs. 48.7% in no‐therapy group, P < 0.001. The in‐segment late loss was also significantly reduced with oral therapy (0.29 ± 0.39 vs. 0.86 ± 0.64 mm, respectively, P < 0.001). Similarly, after six months, patients in the oral rapamycin group also showed a significantly lower incidence of TLR and TVR (7% vs. 22.7%, respectively, P = 0.039) and MACE (7% vs. 22.7%, respectively, P = 0.039). Conclusions : This study showed that the administration of oral rapamycin (2 mg/day, without loading dose) during 30 days after stent implantation significantly reduces angiographic and clinical parameters of restenosis. © 2009 Wiley‐Liss, Inc. 相似文献
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Vlahović M Mataruga VP Ilijin L Mrdaković M Mirčić D Todorović D Lazarević J 《Ecotoxicology (London, England)》2012,21(2):370-378
Many biochemical, physiological and histological criteria have been used as indicators of exposures and effects of the contaminants.
These changes can indicate the response of an organism to a specific environmental stressor. In the present paper, the effect
of the acute and chronic exposure to cadmium as well as recovery from two cadmium concentrations (10 and 30 μgCd/g dry food)
on gypsy moth (Lymantria dispar) midgut esterases was investigated. The influence of cadmium on trait plasticity was also examined. Esterases showed great
sensitivity to low metal concentrations during acute and chronic treatments. Their activities during short-term exposure and
after recovery significantly depended on cadmium concentrations. The esterases had greater index of plasticity during chronic
treatments with 10 and 30 μgCd/dry food. Five esterase isoforms between 64 and 250 kDa were detected. Isoforms of esterases
exposed to any of the two cadmium effects differed among several egg-masses. Isozymes were distinguished in one egg-mass during
different cadmium treatments. We conclude that these enzymes could be considered potential and sensitive non-selective biomarkers
for the presence of cadmium in food. 相似文献
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Vanessa A. Fitsanakis Kimberly N. Thompson Sarah E. Deery Dejan Milatovic Zak K. Shihabi Keith M. Erikson Russell W. Brown Michael Aschner 《Neurotoxicity research》2009,15(2):167-178
Iron deficiency (ID) is especially common in pregnant women and may even persist following childbirth. This is of concern in light of reports demonstrating that ID may be sufficient to produce homeostatic dysregulation of other metals, including manganese (Mn). These results are particularly important considering the potential introduction of the Mn-containing gas additive, methyl cyclopentadienyl manganese tricarbonyl (MMT), in various countries around the world. In order to model this potentially vulnerable population, we fed female rats fed either control (35 mg Fe/kg chow; 10 mg Mn/kg chow) or low iron/high-manganese (IDMn; 3.5 mg Fe/kg chow; 100 mg Mn/kg chow) diet, and examined whether these changes had any long-term behavioral effects on the animals’ spatial abilities, as tested by the Morris water maze (MWM). We also analyzed behavioral performance on auditory sensorimotor gating utilizing prepulse inhibition (PPI), which may be related to overall cognitive performance. Furthermore, brain and blood metal levels were assessed, as well as regional brain isoprostane production. We found that treated animals were slightly ID, with statistically significant increases in both iron (Fe) and Mn in the hippocampus, but statistically significantly less Fe in the cerebellum. Additionally, isoprostane levels, markers of oxidative stress, were increased in the brain stem of IDMn animals. Although treated animals were indistinguishable from controls in the PPI experiments, they performed less well than controls in the MWM. Taken together, our data suggest that vulnerable ID populations exposed to high levels of Mn may indeed be at risk of potentially dangerous alterations in brain metal levels which could also lead to behavioral deficits. 相似文献
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Novel trends in high-throughput screening 总被引:1,自引:0,他引:1
Lead discovery by high-throughput screening (HTS) has evolved into a mature scientific discipline in modern drug discovery since its beginning about 10–15 years ago. Owing to the strong efforts in automation and miniaturization, even relatively large compound collections of over one million compounds or more can be screened against a large number of biological targets in relatively short time and at relatively low cost compared to the efforts of just 5 or 10 years ago. This was only possible with the concomitant development of high-quality readout technologies for highly miniaturized screening. Whereas most of the conventional drug targets can be approached via current HTS-readout technologies, the challenge goes toward the hitherto non-tractable families of drug targets. Future trends will focus strongly toward these novel target classes such as ion channels, transporters, protein–protein interactions, among many others. It will be essential to make proper readout technologies and adequate chemical libraries available for these target classes. Chemical libraries derived from natural products, but also derived from combinatorial chemistry and automated synthesis will be a key prerequisite for success in the field, as long as enough diversity and drug-like properties are included in these chemical libraries [25]. The proper readout technologies for screening of large chemical libraries have seen strong advances in recent years [[2], [7] and [22••]], nevertheless none of these technologies is void of artifacts, in particular artifacts derived from the inherent physical nature of chemical compounds in aqueous buffer [11••]. We therefore propose that future lead discovery should pay more attention toward unambiguous identification of these compound related artifacts and toward efficient removal of these false-positive compounds from the HTS hit-lists. We strongly recommend the use of biophysical and enzymological studies in the HTS hit-list follow-up phase (‘hit validation’) in order to deliver information of the highest possible quality for subsequent hit-to-lead studies. Finally, the science and art of HTS has evolved in various phases from its beginning in the early 1990s toward today's state-of-the-art operation in lead discovery. During these 15 years, one can distinguish three phases (‘generations’) of HTS operations: during the first phase, HTS has been just the same as laboratory screening, albeit at much larger capacity; in the second phase (‘second generation HTS’), HTS has evolved toward more sophisticated assay development/adaptation, more toward dedicated tool production, but also more toward counter-screening and hit-list follow-up; in the current phase (‘third generation HTS’) we see much more flexibility with regards to the applied processes for lead discovery, a stronger focus on quality and validation of the obtained results and a better awareness for choosing a proper lead finding strategy in a target-by-target specific manner.Taken together, we can conclude that better flexibility and creativity, more quality and the use of project-related, tailor-made lead finding strategies in the discovery process will become the key drivers for the successful application of high-throughput screening in the Pharmaceutical, Biotech, and Academic drug discovery programs of the future.
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:- • of special interest
- •• of outstanding interest
38.
Vesna Peri - Mataruga Dejan Mir
i Milena Vlahovi Marija Mrdakovi Dajana Todorovi Darko Stevanovi Verica Miloevi 《Appetite》2009,53(1):147-150
Ghrelin is a 28-amino acid peptide which has significant effects on animal appetite, thus influencing body mass. The aim of our study was to examine the effects of ghrelin on the feeding behavior and physiology 4th instar caterpillars of the pest insect, Lymantria dispar L. Treatment of 4th instar caterpillars with four subpicomolar amounts of ghrelin had a positive influence on daily food intake, frass elimination, body mass. Also, locomotor activity increased, while stadium duration decreased in treated caterpillars. The similarity between the effects of ghrelin on caterpillar physiology and those in mammals suggests that using this model system for further studies of neuroendocrinological processes underlying feeding could lead to essential information about more complex organisms. 相似文献
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