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21.
22.
陈世铭 《军医进修学院学报》1989,(4)
本文应用实验性重症肌无力模型研究了7种新的胆碱酯酶抑制剂对实验性重症肌无力的治疗作用,其中包括6种二甲氨基甲酸烷氧(烷硫)基苯酯及1种中草药提取物,大多数化合物对乙酰胆碱酯酶有较强的抑制作用,并见到有不同程度的治疗效果。二甲氨基甲酸-3-叔丁基-4〔2-(1-哌啶基)乙氧基〕苯酯不仅明显改善肌无力症状,而且毒性小、副作用较新斯的明轻,值得进一步研究。 相似文献
23.
Antiproliferative Activity Against MCF‐7 Breast Cancer Cells by Diamino‐Triazaspirodiene Antifolates
Xiang Ma Renee Ser‐Peng Woon Paul Chi‐Lui Ho Wai‐Keung Chui 《Chemical biology & drug design》2009,74(3):322-326
Two triazaspirodienes, having similar phenoxy propyloxy side chain, were identified as potent mammalian dihydrofolate reductase inhibitors; one having a 6,5‐spiro bicyclic ring system (IC50 = 2.3 nm ) and the other a 6,6‐spiro bicyclic system (IC50 = 6.9 nm ). They also showed more than 50% antiproliferative activity against the MCF‐7 breast cancer cells at 20 μm . This study demonstrated the potential lead of the diamino‐triazaspirodienes in anticancer chemotherapeutical agents’ discovery. 相似文献
24.
A review of serotonin toxicity data: implications for the mechanisms of antidepressant drug action. 总被引:2,自引:0,他引:2
P Ken Gillman 《Neuropsychopharmacology》2006,59(11):1046-1051
Data now exist from which an accurate definition for serotonin toxicity (ST), or serotonin syndrome, has been developed; this has also lead to precise, validated decision rules for diagnosis. The spectrum concept formulates ST as a continuum of serotonergic effects, mediated by the degree of elevation of intrasynaptic serotonin. This progresses from side effects through to toxicity; the concept emphasizes that it is a form of poisoning, not an idiosyncratic reaction. Observations of the degree of ST precipitated by overdoses of different classes of drugs can elucidate mechanisms and potency of drug actions. There is now sufficient pharmacological data on some drugs to enable a prediction of which ones will be at risk of precipitating ST, either by themselves or in combinations with other drugs. This indicates that some antidepressant drugs, presently thought to have serotonergic effects in animals, do not exhibit such effects in humans. Mirtazapine is unable to precipitate serotonin toxicity in overdose or to cause serotonin toxicity when mixed with monoamine oxidase inhibitors, and moclobemide is unable to precipitate serotonin toxicity in overdose. Tricyclic antidepressants (other than clomipramine and imipramine) do not precipitate serotonin toxicity and might not elevate serotonin or have a dual action, as has been assumed. 相似文献
25.
F. Tribut B. Lapied A. Duval M. Pelhate 《Pflügers Archiv : European journal of physiology》1991,419(6):665-667
Short-term culture of isolated adult dorsal unpaired median (DUM) neurons of the cockroach Periplaneta americana has been used to study the evolution of the sodium current during the time in culture after axotomy and deafferentation treatment. An increase in the maximum peak amplitude of the sodium current recorded under voltage-clamp conditions with the patch-clamp technique in the whole-cell recording configuration, was only observed between 24h and 72h (75%) without any modification of the kinetics and the voltage-dependence of the current. A decrease in the level of foetal calf serum in the culture medium reduces the amplitude of the sodium current on all days but does not affect its time-course of development which was on the contrary completely abolished by both protein synthesis inhibitors, actinomycin D and cycloheximide. The results obtained in these neurons strongly suggest that a neosynthesis of sodium channel proteins is involved in the evolution of the sodium current induced by axotomy and deafferentation. 相似文献
26.
J. Boldt H. A. Adams B. Zickmann D. Kling G. Hempelmann 《European journal of clinical pharmacology》1990,38(5):431-436
Summary The release of endogenous catecholamines in aorto-coronary bypass graft patients receiving either 0.5 mg/kg enoximone (n=10), 4.0 mg/kg theophylline (n=10) or saline solution (control,n=10) has been studied, as well as certain haemodynamic parameters. Adrenaline (A) and noradrenaline (NA) concentrations were
not significantly changed by the administration of enoximone. Theophylline caused a small increase in NA (+ 40% in the 1st
min) and a marked increase in A (approximately + 7000% in the 1st min), which still remained elevated at the end of the investigation
period (+ 220% in the 30th min). The major haemodynamic effects of enoximone were a significant increase in cardiac index
(CI; + 35%) and a decrease in pulmonary capillary wedge pressure (PCWP; −27%), pulmonary artery pressure (PAP; −21%), RVEDV
and RVESV, while the heart rate (HR) remained almost unchanged. The dominant haemodynamic effects of theophylline were an
increase in HR (+ 26%; arrhythmia in 3 patients), PAP (+ 22%), and RVEDV (+ 19%), while REVESV (+ 26%), MAP (−16%), CI (−14%),
and RVEF (−15%) fell significantly.
It is concluded that the haemodynamic actions of enoximone are not mediated by catecholamine release, whereas the adverse
cardiovascular effects of theophylline might partly be explained by the significant increase in plasma adrenaline. 相似文献
27.
We describe how adverse drug reactions (ADRs) can play an important role in pharmaceutical research and drug development. Not only do ADRs represent the risks and drawbacks associated with drugs but they can also be related to other knowledge available in pharmaceutical and medical research. We offer a model that can be used to systematically map the pathways through which ADRs can lead to innovative research. These pathways include chemical, therapeutic or pathophysiological steps that can be taken to arrive at new knowledge based on ADRs. We used the development of angiotensin-converting enzyme inhibitors, especially captopril, as a case study. The similarity between the ADR profiles of captopril and penicillamine was a starting point for further innovation. Historical analysis shows that in several instances research in the field of angiotensin-converting enzyme inhibitors has been triggered by ADRs. The model presented here might be applicable to other areas of innovative drug research. 相似文献
28.
29.
30.
Summary Estrogen has an important role in stimulating the growth of breast carcinomas. Inhibition of estrogen production is therefore a logical treatment strategy. A number of selective inhibitors have been developed against aromatase, a cytochrome P-450 enzyme which catalyzes the rate limiting step in the biosynthesis of estrogens. The mechanisms of the aromatase reaction, current knowledge of the enzyme, and regulation of its expression are discussed as the basis for inhibitor development. Two classes of aromatase inhibitors, steroidal and non-steroidal compounds, are now coming into use. Among the steroid substrate analogues, 4-hydroxyandrostenedione (4-OHA) has been shown to be effective in breast cancer patients with advanced disease and was recently approved for treatment in the United Kingdom. Several different classes of compounds which act as aromatase inhibitors are currently in clinical trials and should provide breast cancer patients with a number of treatment options. Among these are highly potent and selective non-steroidal inhibitors which have recently been found to suppress plasma and urinary estrogens over 95% in breast cancer patients. The potency of these newer aromatase inhibitors provides the opportunity to determine whether complete suppression of estrogen production and action will result in enhanced tumor regression. 相似文献