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Michał Seweryn Karbownik Paweł Gunerka Paweł Turowski Maciej Wieczorek Edward Kowalczyk Wojciech Łężak Tadeusz Pietras 《Pharmacological reports : PR》2018,70(2):346-349
Background
Catalytic subunit delta of phosphoinositide 3-kinase, p110δ, encoded by the PIK3CD gene, was recently proposed as a target for pharmacological treatment of schizophrenia. Current antipsychotic drugs were found to decrease the mRNA expression of PIK3CD, but the mechanism of this process is not known. The aim of the study was to elucidate the mechanism by which antipsychotic drugs affect the mRNA expression of PIK3CD.Methods
The direct effect of haloperidol, clozapine, olanzapine, quetiapine and amisulpride on p110δ enzymatic activity was tested with a kinase assay, and the results were referenced against data on the mRNA expression of PIK3CD.Results
Haloperidol, clozapine, olanzapine and quetiapine, but not amisulpride, at the concentration of 20–80?μM, were found to significantly increase enzymatic activity of p110δ by up to two times in a dose-dependent manner. Linear regression analysis revealed that more than 40% of the variance in antipsychotic drugs-induced changes in the expression of PIK3CD mRNA was explained only by changes in antipsychotic drug-regulated p110δ enzymatic activity (p?=?0.011).Conclusions
Antipsychotic drugs differentially increase the enzymatic activity of p110δ. This effect is associated with that of mRNA expression of the PIK3CD gene. Drug-enzyme interaction may explain the effect of antipsychotic drugs on the expression of PIK3CD mRNA, however, further studies are needed to investigate this hypothesis. 相似文献93.
股四头肌肌力减弱、收缩障碍、伸膝障碍是膝关节术后常见的临床表现,这一现象被称为关节源性肌肉抑制(AMI)。AMI会导致肌力训练无效、肌肉萎缩、运动功能下降,甚至骨关节炎的发生。然而,关于AMI的原理和治疗国内关注和报道较少。本文通过对中国知网、万方、维普、Pubmed、CINAHL、EMBASE、Cochrane Library电子数据进行全面的检索,仅纳入同行评议文章,用描述性系统综述的方法简述膝关节术后股四头肌抑制的原理,总结目前国内外股四头肌抑制的治疗方法,以期为临床工作提供借鉴。 相似文献
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《Burns : journal of the International Society for Burn Injuries》2022,48(3):713-722
BackgroundRisk factors and mechanisms of injury may change over time. Since knowledge on aetiology of severe burn incidents in children under 5 years of age in the Netherlands is outdated, this study aimed to identify current risk factors and mechanisms of severe burn injury in children under 5 years of age in the Netherlands to direct future prevention campaigns.MethodsInformation on personal-, environmental- and behavioural circumstances as well as the mechanism of burn injury was prospectively collected in all burn centres during one year from patient records and structured interviews with parents.ResultsBoys around 18 months of age, who, while in upright position, pulled down a cup of hot tea over themselves, were overrepresented. Children in families with more children, having a migration background, living in urbanised neighborhoods or with a low socioeconomic status (SES) are at increased risk for severe burn injury. Most incidents happened in their own home with the parents in close proximity to the child.ConclusionOutcomes of this prospective cohort study provide up-to-date and extensive knowledge on the aetiology of severe burn incidents in children under 5 years of age in the Netherlands, and provide directions for prevention policy and campaigns. 相似文献
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A Bayesian integrated testing strategy (ITS) approach, aiming to assess skin sensitization potency, has been presented, in which data from various types of in vitro assays are integrated and assessed in combination for their ability to predict in vivo skin sensitization data. Here we discuss this approach and compare it to our quantitative mechanistic modeling (QMM) approach based on physical organic chemistry. The main findings of the Bayesian study are consistent with our chemistry‐based approach and our previously published assessment of the key determinants of sensitization potency, in particular the relatively high predictive value found for chemical reactivity data and the relatively low predictive value for bioavailability parameters. As it stands at present the Bayesian approach does not utilize the full range of predictive capability that is already available, and aims only to assign potency categories rather than numerical potency values per se. In contrast, for many chemicals the QMM approach can already provide numerical potency predictions. However, the Bayesian approach may have potential for those chemicals where a chemistry modeling approach cannot provide a complete answer (e.g. pro‐electrophiles whose in cutaneo activation cannot currently be modeled confidently). Nonetheless, our main message is of the importance of leveraging chemistry insights and read‐across approaches to the fullest extent possible. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
99.
Cheng Wang Rennan Feng Yuanyuan Li Yunbo Zhang Zhen Kang Wei Zhang Dian-Jun Sun 《Toxicology letters》2014
Chronic arsenicosis induced by excessive arsenic intake can cause damages to multi-organ systems, skin cancer and various internal cancers. However, the key metabolic changes and biomarkers which can reflect these changes remain unclear resulting in a lack of effective prevention and treatments. The aim of this study is to determine the impact of chronic arsenic exposure on the metabolism of organism, and find the metabolites changes by using metabolomic techniques. Thirty male Wistar rats were randomly divided into three groups. The arsenite was administered in water, and the doses were 0, 10, and 50 mg/L, respectively. The exposure lasted for 6 months. The endogenous metabolite profile of serum was investigated by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Partial least squares discriminant analysis (PLS-DA) enabled clusters to be visualized. Nine serum principal metabolites contributing to the clusters were identified, which were CPA (18:2(9Z,12Z)/0:0), LysoPC (14:0), LysoPC (18:4 (6Z,9Z,12Z,15Z)), LysoPC (P-18:0), l-palmitoylcarnitine, LysoPC (20:2(11Z,14Z)) in positive ESI mode and deoxygcholylglycine, LysoPE (0:0/20:2(11Z,14Z)), 15(S)-hydroxyeicosatrienoic acid in negative ESI. These changes of metabolites in rats suggested the changed metabolism in rats exposed to arsenic. These findings may further aid diagnose and serve as targets for therapeutic intervention of arsenicosis. 相似文献
100.
目的:为过期药品回收处理机制的建立提供理论依据。方法:以药品生产企业为过期药品回收处理的主体,通过经济学中外部性和供需曲线理论进行论证,并参考实例比较通过征收矫正税和采取激励补贴机制两种途径对过期药品回收处理主体的影响,以此来选取合理的过期药品回收方式。结果与结论:如果采取向生产企业征收矫正税的方式,可能会打击部分生产企业主动回收过期药品的积极性;而采取激励补贴机制则可能鼓励更多的生产企业参与到过期药品的回收处理活动中,解决当前药品回收中存在的问题,使过期药品回收活动中产生的公共事务的外部性问题变负为正,增加社会总福利。因此,采取激励补贴机制具有经济学合理性并切合当前实际,可作为建立过期药品长期回收机制设计时重要的参考依据。 相似文献