全文获取类型
收费全文 | 6346篇 |
免费 | 468篇 |
国内免费 | 32篇 |
专业分类
耳鼻咽喉 | 52篇 |
儿科学 | 102篇 |
妇产科学 | 64篇 |
基础医学 | 1046篇 |
口腔科学 | 44篇 |
临床医学 | 772篇 |
内科学 | 1736篇 |
皮肤病学 | 88篇 |
神经病学 | 564篇 |
特种医学 | 225篇 |
外科学 | 853篇 |
综合类 | 20篇 |
预防医学 | 502篇 |
眼科学 | 45篇 |
药学 | 367篇 |
中国医学 | 9篇 |
肿瘤学 | 357篇 |
出版年
2023年 | 31篇 |
2022年 | 44篇 |
2021年 | 176篇 |
2020年 | 89篇 |
2019年 | 162篇 |
2018年 | 182篇 |
2017年 | 104篇 |
2016年 | 117篇 |
2015年 | 179篇 |
2014年 | 252篇 |
2013年 | 299篇 |
2012年 | 493篇 |
2011年 | 478篇 |
2010年 | 277篇 |
2009年 | 254篇 |
2008年 | 435篇 |
2007年 | 441篇 |
2006年 | 426篇 |
2005年 | 445篇 |
2004年 | 406篇 |
2003年 | 404篇 |
2002年 | 395篇 |
2001年 | 59篇 |
2000年 | 50篇 |
1999年 | 84篇 |
1998年 | 89篇 |
1997年 | 59篇 |
1996年 | 46篇 |
1995年 | 49篇 |
1994年 | 43篇 |
1993年 | 18篇 |
1992年 | 24篇 |
1991年 | 22篇 |
1990年 | 35篇 |
1989年 | 25篇 |
1988年 | 26篇 |
1987年 | 19篇 |
1986年 | 18篇 |
1985年 | 10篇 |
1984年 | 11篇 |
1983年 | 8篇 |
1982年 | 8篇 |
1981年 | 4篇 |
1979年 | 4篇 |
1978年 | 4篇 |
1975年 | 4篇 |
1973年 | 7篇 |
1972年 | 3篇 |
1971年 | 6篇 |
1966年 | 3篇 |
排序方式: 共有6846条查询结果,搜索用时 15 毫秒
991.
992.
Le Minor O Germani Y Chartier L Lan NH Lan NT Duc NH Laureillard D Fontanet A Sar B Saman M Chan S L'Her P Mayaud C Vray M 《Journal of acquired immune deficiency syndromes (1999)》2008,48(5):620-627
OBJECTIVES: To identify predictors of Pneumocystis jiroveci pneumonia (PCP) or pulmonary tuberculosis (TB) in acid-fast bacillus smear-negative HIV-infected patients and to develop clinical prediction rules. DESIGN: A cohort study conducted in consecutive hospitalized Asian patients. METHODS: Multivariate analyses were performed on the Cambodian sample to determine clinical, radiological, and biological predictors of PCP or TB at hospital admission. The Vietnamese sample was kept for independent validation. RESULTS: In Cambodia, the gold standard technique for TB and PCP were fulfilled in 172 (27 cases) and 160 (84 cases) patients, respectively. For TB, independent predictors included the following: headache [odds ratio (OR) 3.0; 95% confidence interval (CI) 1.04 to 8.6], localized radiological opacity (OR 5.8; 95% CI 1.9-17.9), and mediastinal adenopathy (OR 10.1; 95% CI 3.5 to 29.0); and for PCP: resting oxygen saturation <90% (OR 3.3; 95% CI 1.3 to 8.5 for resting arterial oxygen saturation >or=80%; and OR 9.1; 95% CI 1.8 to 44.5 for resting arterial oxygen saturation <80%), trimethoprim-sulphamethoxazole prophylaxis (OR 0.1; 95% CI 0.04 to 0.6), and diffuse radiological shadowing (OR 7.0; 95% CI 2.7 to 18.6). PCP risk predicted by a score based on these 3 factors ranged from 3% to 92% (Cambodia). When tested on Vietnamese patients (n = 69, 38 with PCP), the score maintained correct predictive ability (c-index = 0.72) but with poor calibration. CONCLUSIONS: The PCP score could provide a useful clinical tool to identify PCP among acid-fast bacillus smear-negative pneumonia and start specific therapy. 相似文献
993.
994.
Genome-wide, high-resolution DNA methylation profiling using bisulfite-mediated cytosine conversion 总被引:1,自引:0,他引:1
Reinders J Delucinge Vivier C Theiler G Chollet D Descombes P Paszkowski J 《Genome research》2008,18(3):469-476
Methylation of cytosines ((m)C) is essential for epigenetic gene regulation in plants and mammals. Aberrant (m)C patterns are associated with heritable developmental abnormalities in plants and with cancer in mammals. We have developed a genome-wide DNA methylation profiling technology employing a novel amplification step for DNA subjected to bisulfite-mediated cytosine conversion. The methylation patterns detected are not only consistent with previous results obtained with (m)C immunoprecipitation (mCIP) techniques, but also demonstrated improved resolution and sensitivity. The technology, named BiMP (for Bisulfite Methylation Profiling), is more cost-effective than mCIP and requires as little as 100 ng of Arabidopsis DNA. 相似文献
995.
996.
Denis Bertin Pierre‐Emmanuel Dufils Isabelle Durand Didier Gigmes Bruno Giovanetti Yohann Guillaneuf Sylvain R. A. Marque Trang Phan Paul Tordo 《Macromolecular chemistry and physics.》2008,209(2):220-224
The effect of the penultimate unit on the C? ON bond homolysis rate constant kd was studied for model alkoxyamines. It was shown that the kd for fragments containing penultimate and antepenultimate units were nicely predicted by the tri‐parametric relationship developed in Macromolecules 2005 , 38, 2638 and Eur. J. Org. Chem. 2006 , 7, 1755 (log kd = ?14.33 + 15.06 × σRS + 20.00 × σI + 6.96 × υ). A striking effect was observed only for a tert‐butyl‐like group as the penultimate unit.
997.
Millan MJ Mannoury la Cour C Chanrion B Dupuis DS Di Cara B Audinot V Cussac D Newman-Tancredi A Kamal M Boutin JA Jockers R Marin P Bockaert J Muller O Dekeyne A Lavielle G 《The Journal of pharmacology and experimental therapeutics》2012,340(3):750-764
Although most antidepressants suppress serotonin (5-HT) and/or noradrenaline reuptake, blockade of 5-HT(2C) receptors and α(2)-adrenoceptors likewise enhances monoaminergic transmission. These sites are targeted by the urea derivative N- [4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-1,2-dihydro-3-H-benzo[e]indole-3-carboxamide (S32212). S32212 was devoid of affinity for monoamine reuptake sites, yet displayed pronounced affinity (pK(i), 8.2) for constitutively active human 5-HT(2CINI) (h5-HT(2CINI)) receptors, behaving as an inverse agonist in reducing basal Gα(q) activation, [(3)H]inositol-phosphate production, and the spontaneous association of h5-HT(2CINI)-Renilla luciferase receptors with β-arrestin2-yellow fluorescent protein. Furthermore, upon 18-h pretreatment, S32212 enhanced the plasma membrane expression of h5-HT(2CINI) receptors as visualized by confocal microscopy and quantified by enzyme-linked immunosorbent assay. Its actions were prevented by the neutral antagonist 6-chloro-5-methyl-N-[6-(2-methylpyridin-3-yloxy)pyridin-3-yl]indoline-1-carboxamide (SB242,084), which also impeded the induction by long-term exposure to S32212 of otherwise absent Ca(2+) mobilization in mouse cortical neurones. In vivo, S32212 blunted the inhibitory influence of the 5-HT(2C) agonist 2-(3-chlorobenzyloxy)-6-(1-piperazinyl)pyrazine (CP809,101) on ventrotegmental dopaminergic neurones. S32212 also blocked 5-HT-induced Gα(q) and phospholipase C activation at the h5-HT(2A) and, less potently, h5-HT(2B) receptors and suppressed the discriminative stimulus properties of the 5-HT(2A) agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane in rats. S32212 manifested marked affinity for human α(2A)- (pK(i) 7.2), α(2B)- (pK(i) 8.2), and α(2C)- (pK(i) 7.4) adrenoceptors, at which it abolished noradrenaline-induced recruitment of Gα(i3), Gα(o), adenylyl cyclase, and extracellular-regulated kinase1/2. Moreover, S32212 dose-dependently abolished the discriminative stimulus effects of the α(2)-adrenoceptor agonist (S)-spiro[(1-oxa-2-amino-3-azacyclopent-2-ene)-4,2'-(1',2',3',4'-tetrahydronaphthalene)] (S18616). Finally, S32212 displayed negligible affinity for α(1A)-adrenoceptors, histamine H(1) receptors, and muscarinic M(1) receptors. In conclusion, S32212 behaves as an inverse agonist at h5-HT(2C) receptors and as an antagonist at human α(2)-adrenoceptors (and h5-HT(2A) receptors). Its promising profile in preclinical models potentially relevant to the treatment of depression is described in J Pharmacol Exp Ther 340:765-780, 2012. 相似文献
998.
Khim N Kim S Bouchier C Tichit M Ariey F Fandeur T Chim P Ke S Sum S Man S Ratsimbasoa A Durand R Ménard D 《Antimicrobial agents and chemotherapy》2012,56(2):863-868
Molecular investigations performed following the emergence of sulfadoxine-pyrimethamine (SP) resistance in Plasmodium falciparum have allowed the identification of the dihydrofolate reductase (DHFR) enzyme as the target of pyrimethamine. Although clinical cases of Plasmodium malariae are not usually treated with antifolate therapy, incorrect diagnosis and the high frequency of undetected mixed infections has probably exposed non-P. falciparum parasites to antifolate therapy in many areas. In this context, we aimed to assess the worldwide genetic diversity of the P. malariae dhfr gene in 123 samples collected in Africa and Asia, areas with different histories of SP use. Among the 10 polymorphic sites found, we have observed 7 new mutations (K55E, S58R, S59A, F168S, N194S, D207G, and T221A), which led us to describe 6 new DHFR proteins. All isolates from African countries were classified as wild type, while new mutations and haplotypes were recognized as exclusive to Madagascar (except for the double mutations at nucleotides 341 and 342 [S114N] found in one Cambodian isolate). Among these nonsynonymous mutations, two were likely related to pyrimethamine resistance: S58R (corresponding to C59R in P. falciparum and S58R in Plasmodium vivax; observed in one Malagasy sample) and S114N (corresponding to S108N in P. falciparum and S117N in P. vivax; observed in three Cambodian samples). 相似文献
999.
1000.
Audrey Coilly Valérie Furlan Bruno Roche Caroline Barau Coralie No?l Laurence Bonhomme-Faivre Teresa Maria Antonini Anne-Marie Roque-Afonso Didier Samuel Anne-Marie Taburet Jean-Charles Duclos-Vallée 《Antimicrobial agents and chemotherapy》2012,56(11):5728-5734
Hepatitis C virus (HCV) recurrence is the most important complication in HCV liver transplant patients. Boceprevir with pegylated interferon and ribavirin (PegIFN/RBV) enabled improvement in sustained virological response rates of patients with genotype 1 HCV. Boceprevir interacts with immunosuppressive therapy (IT) by inhibiting the cytochrome P450 3A enzyme. Our aim was to study interactions and assess the safety of boceprevir in the context of HCV recurrence. Boceprevir (800 mg three times a day) initiated after a 4-week lead-in phase was associated with cyclosporine (three patients), tacrolimus (two patients), and everolimus (one patient) in five liver transplant patients with genotype 1 HCV infection who experienced HCV recurrence. The mean follow-up period after HCV therapy was 14.8 ± 3.1 weeks. Estimated oral clearances of IT decreased on average by 50%, requiring reduced dosing regimens. Anemia occurred in all patients, with a mean fall in hemoglobin levels between baseline and week 12 of 3.12 ± 2.27 g/dl. All patients required administration of β-erythropoietin (n = 5), three needed ribavirin dose reduction, and one needed a blood transfusion. A virological response was observed in all patients (mean HCV viral load [HVL] decrease at week 12, 6.64 ± 0.35 log10 IU/ml). These preliminary results in liver transplant patients with HCV recurrence demonstrate the feasibility and safety of coadministration of boceprevir and IT. 相似文献