全文获取类型
收费全文 | 74215篇 |
免费 | 41214篇 |
国内免费 | 2篇 |
专业分类
耳鼻咽喉 | 1475篇 |
儿科学 | 4198篇 |
妇产科学 | 492篇 |
基础医学 | 15190篇 |
口腔科学 | 5037篇 |
临床医学 | 12102篇 |
内科学 | 22446篇 |
皮肤病学 | 7408篇 |
神经病学 | 13061篇 |
特种医学 | 2104篇 |
外科学 | 13441篇 |
综合类 | 2篇 |
一般理论 | 21篇 |
预防医学 | 3973篇 |
眼科学 | 1215篇 |
药学 | 5386篇 |
中国医学 | 1006篇 |
肿瘤学 | 6874篇 |
出版年
2023年 | 12篇 |
2022年 | 21篇 |
2021年 | 1212篇 |
2020年 | 5006篇 |
2019年 | 10769篇 |
2018年 | 10014篇 |
2017年 | 11390篇 |
2016年 | 12030篇 |
2015年 | 11863篇 |
2014年 | 11733篇 |
2013年 | 12185篇 |
2012年 | 3877篇 |
2011年 | 3799篇 |
2010年 | 8792篇 |
2009年 | 5159篇 |
2008年 | 1864篇 |
2007年 | 706篇 |
2006年 | 767篇 |
2005年 | 548篇 |
2004年 | 556篇 |
2003年 | 578篇 |
2002年 | 687篇 |
2001年 | 741篇 |
2000年 | 665篇 |
1999年 | 245篇 |
1998年 | 18篇 |
1997年 | 16篇 |
1996年 | 19篇 |
1995年 | 18篇 |
1994年 | 17篇 |
1993年 | 8篇 |
1992年 | 15篇 |
1991年 | 10篇 |
1990年 | 9篇 |
1989年 | 5篇 |
1988年 | 13篇 |
1987年 | 8篇 |
1986年 | 2篇 |
1985年 | 5篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1979年 | 7篇 |
1978年 | 3篇 |
1977年 | 5篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1971年 | 2篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Naruhiro Ishida Noriko Odani‐Kawabata Atsushi Shimazaki Hideaki Hara 《Cardiovascular therapeutics》2006,24(1):1-10
Elevated intraocular pressure (IOP) is one of the most important risk factors for the development of glaucoma, which is a progressive optic neuropathy. Lowering IOP is currently the only therapeutic approach to the therapy of glaucoma. Since the use of pilocarpine eye drops for glaucoma treatment was reported in the late 1870s, academic researchers and pharmaceutical companies attempted to discover new drugs with more potent, prolonged, and safer IOP‐reducing effects. These persistent efforts finally paid off, and prostanoids with FP‐receptor agonist activity were found to be very potent IOP‐lowering agents. To date, three prostanoids (latanoprost, travoprost and bimatoprost) have been launched in many countries, and now a new FP‐receptor agonist, tafluprost, is entering clinical development. All of these prostanoids are superior to the β‐adrenoceptor antagonists in their IOP‐lowering efficacy, and no severe side effects have been reported in their long‐term clinical use. In addition, tafluprost may be expected to improve ocular blood flow. Hence, prostanoids currently occupy center stage among glaucoma medications. It cannot be denied that in terms of efficacy, safety, patient compliance, and medical economy prostanoids are currently the first‐line medicines among ocular antihypertensive drugs. 相似文献
992.
993.
Dora Koller Carmen Belmonte Miriam Saiz‐Rodríguez Pablo Zubiaur Manuel Romn Dolores Ochoa Francisco Abad‐Santos 《Basic & clinical pharmacology & toxicology》2020,126(3):236-246
Aripiprazole treatment in schizophrenic patients was previously associated with lower or normalized prolactin levels. Genetic variants in cytochrome P450 (CYP) (CYP2D6), dopamine receptor (DRD2, DRD3) and serotonin receptor (HTR2A, HTR2C) genes were previously associated with antipsychotic‐induced hyperprolactinaemia. Our aim was to evaluate whether aripiprazole affects prolactin secretion and its relationship with pharmacogenetics. Thirty‐one healthy volunteers receiving a 10‐mg single oral dose of aripiprazole were genotyped for 12 polymorphisms in CYP2D6, DRD2, DRD3, HTR2A and HTR2C genes by qPCR. Aripiprazole and dehydro‐aripiprazole plasma concentrations were measured by HPLC‐MS/MS. Prolactin concentrations of the 31 volunteers taking aripiprazole and 12 volunteers receiving ibuprofen were determined by ELISA. Prolactin concentrations after ibuprofen intake were considered as control, since it is known to cause no effect. Prolactin concentrations were slightly higher in the aripiprazole group compared to the ibuprofen group. All prolactin pharmacokinetic parameters were higher in females than in males. CYP2D6 poor and intermediate metabolizers had notably higher prolactin Cmax and AUC0‐12 than normal and ultrarapid metabolizers. The DRD3 rs6280 polymorphism affected prolactin levels: volunteers carrying Ser/Ser genotype had significantly lower prolactin levels than volunteers carrying the Gly allele. Furthermore, HTR2C rs3813929 C/C homozygotes had significantly lower prolactin levels than T allele carriers. Nevertheless, aripiprazole did increase prolactin levels compared to ibuprofen. 相似文献
994.
Abd El Kader Ait Tayeb Laurent Becquemont Khalil El‐Asmar Kaïna Mahmoudi Romain Colle Severine Trabado Florence Gressier Bruno Feve Emmanuelle Corruble Cline Verstuyft 《Basic & clinical pharmacology & toxicology》2020,126(3):289-295
Two thirds of patients suffering from a major depressive episode (MDE) do not reach a complete response with antidepressant drugs. This lack of response is due to several factors, including genetic determinants. Since major depressive disorder is associated with inflammatory and oxidative stress abnormalities, the metabolism of superoxide anions might be involved in non‐response to antidepressant drugs. Superoxide anions are metabolized by manganese‐dependent superoxide dismutase (SOD2) in the mitochondria. A functional genetic polymorphism (SOD2, rs4880), responsible of a 40% reduction in enzyme activity, is associated with anti‐inflammatory response of rosuvastatin. We investigated the association of ala‐allele of SOD2 rs4880 and both antidepressant efficacy and inflammatory parameters in patients treated for a MDE with antidepressant drugs. The Hamilton Depression Rating Scale (HDRS) score and levels of plasma CRP and inflammatory cytokines were assessed at baseline, one month (M1), 3 months (M3) and 6 months (M6) after antidepressant treatment. They were compared according to SOD2 genetic polymorphism. Of the 484 patients studied, 361 (74.6%) carried the ala‐allele (Ala group), 123 (25.4%) of them had Val/Val genotype (Val/Val group). No significant difference was observed between the Ala and Val/Val groups neither for baseline clinical characteristics, nor for HDRS scores, response/remission rates, plasma CRP and cytokine levels throughout the study. The rs4880 SOD2 genetic polymorphism was not associated with the clinical response and cytokines levels after antidepressant treatment. These data suggest that SOD2 is not a major genetic determinant of antidepressant response. Other genes of the oxidative stress pathways should be explored in further studies. 相似文献
995.
Israa A. Seliem Siva S. Panda Adel S. Girgis Yosra I. Nagy Riham F. George Walid Fayad Nehmedo G. Fawzy Tarek S. Ibrahim Amany M. M. Al‐Mahmoudy Rajeev Sakhuja Zakaria K. M. Abdel‐samii 《Chemical biology & drug design》2020,95(2):248-259
A series of new fluoroquinolone conjugates 8a–g and 9a–f were synthesized via benzotriazole‐mediated synthetic approach with good yield and purity. Some of the synthesized analogs exhibited significant antibacterial properties against Escherichia coli and Staphylococcus aureus with potency higher than that of the parent drugs through in vitro standard bioassay procedure (conjugates 8c and 8d reveal antimicrobial properties with potency 1.9, 61.9, 20.7 and 2.4, 37.1, 8.3 folds relative to the parent antibiotic 6 against E. coli, S. aureus, and Enterococcus faecalis, respectively). The observed experimental data were supported by enzymatic DNA gyrase inhibitory property. Developed BMLR‐QSAR model validates the observed experimental data and recognizes the parameters responsible for the enhanced antibacterial properties. 相似文献
996.
Vivian Delcourt Patrice Garcia Benjamin Chabot Benoit Loup Pierre Remy Marie‐Agns Popot Ludovic Bailly‐Chouriberry 《Drug testing and analysis》2020,12(6):763-770
Recombinant human erythropoietin (rHuEPO) belongs to the therapeutic class of erythropoiesis stimulating agents (ESAs) due to its implication in the creation pathway of red blood cells and thus enhancement of oxygenation. Because of this bioactivity, rHuEPO has been considered as a major doping agent in sports competitions for decades. Over the years, doping control laboratories designed several analytical strategies applied to human and animal samples to highlight any misuse. Even though multiple analytical approaches have been reported, none has yet been dedicated to racing camels. Here, we describe an analytical strategy to test camel plasma samples at screening using an ELISA assay and a targeted nano‐liquid chromatography–high‐resolution tandem mass spectrometry for confirmatory analysis. The method was validated and has been successfully applied to post‐race samples, allowing the detection of a positive case of rHuEPO administration. 相似文献
997.
998.
999.
Jia‐Li Wang Kai‐Xin Wang Tian‐Lei Han Jin‐Mei Li Xu He Rui‐Xue Rong Zhi‐Ran Cao Xiao‐Liu Li Ke‐Rang Wang 《Chemical biology & drug design》2020,96(2):870-877
Camptothecin (CPT) and its analogues show potent antitumour activity. However, poor water solubility and severe side effects have restricted their applications in clinical practice. In this paper, a novel self‐assembly based on camptothecin and carbamoylmannose conjugates ( CPT‐Man ) was constructed. The self‐assembly increased the water solubility of camptothecin to 0.64 mg/ml and antitumour activity. Moreover, CPT‐Man could induce obvious cancer cell apoptosis. This work provides a new approach for exploring carbohydrate‐modified antitumour properties by self‐assembled CPT drugs. 相似文献
1000.
Sascha Münster‐Müller Isabelle Matzenbach Thomas Knepper Ralf Zimmermann Michael Pütz 《Drug testing and analysis》2020,12(1):119-126
Vaping of synthetic cannabinoids via e‐cigarettes is growing in popularity. In the present study, we tentatively identified 12 by‐products found in a pure sample of the synthetic cannabinoid Cumyl‐5F‐PINACA (1‐(5‐fluoropentyl)‐N‐(2‐phenylpropan‐2‐yl)‐1H‐indazole‐3‐carboxamide), a prevalent new psychoactive substance (NPS) in e‐liquids, via high‐resolution mass spectrometry fragmentation experiments (HRMS/MS). Furthermore, we developed a procedure to reproducibly extract this synthetic cannabinoid and related by‐products from an e‐liquid matrix via chloroform and water. The extracts were submitted to flash chromatography (F‐LC) to isolate the by‐products from the main component. The chromatographic impurity signature was subsequently assessed by ultra‐high‐performance liquid chromatography coupled to mass spectrometry (UHPLC–MS) and evaluated by automated integration. The complete sample preparation sequence (F‐LC + UHPLC–MS) was validated by comparing the semi‐quantitative signal integrals of the chromatographic impurity signatures of five self‐made e‐liquids with varying concentrations of Cumyl‐5F‐PINACA [0.1, 0.2, 0.5, 0.7 and 1.0% (w/w)], giving an average relative standard deviation of 6.2% for triplicate measurements of preparations of the same concentration and 10.5% between the measurements of the five preparations with different concentrations. Lastly, the chromatographic signatures of 14 e‐liquid samples containing Cumyl‐5F‐PINACA from police seizures and Internet test purchases were evaluated via hierarchical cluster analysis for potential links. For the e‐liquid samples originating from test purchases, it was found that the date of purchase, the identity of the online shop, and the brand name are the critical factors for clustering of samples. 相似文献