全文获取类型
收费全文 | 4860篇 |
免费 | 188篇 |
国内免费 | 28篇 |
专业分类
耳鼻咽喉 | 80篇 |
儿科学 | 119篇 |
妇产科学 | 176篇 |
基础医学 | 471篇 |
口腔科学 | 55篇 |
临床医学 | 352篇 |
内科学 | 1313篇 |
皮肤病学 | 84篇 |
神经病学 | 663篇 |
特种医学 | 147篇 |
外科学 | 673篇 |
综合类 | 9篇 |
一般理论 | 2篇 |
预防医学 | 213篇 |
眼科学 | 143篇 |
药学 | 225篇 |
中国医学 | 22篇 |
肿瘤学 | 329篇 |
出版年
2023年 | 62篇 |
2022年 | 91篇 |
2021年 | 145篇 |
2020年 | 94篇 |
2019年 | 104篇 |
2018年 | 139篇 |
2017年 | 92篇 |
2016年 | 121篇 |
2015年 | 116篇 |
2014年 | 190篇 |
2013年 | 232篇 |
2012年 | 366篇 |
2011年 | 348篇 |
2010年 | 210篇 |
2009年 | 204篇 |
2008年 | 331篇 |
2007年 | 290篇 |
2006年 | 267篇 |
2005年 | 298篇 |
2004年 | 230篇 |
2003年 | 219篇 |
2002年 | 193篇 |
2001年 | 68篇 |
2000年 | 56篇 |
1999年 | 53篇 |
1998年 | 39篇 |
1997年 | 28篇 |
1996年 | 30篇 |
1995年 | 39篇 |
1994年 | 30篇 |
1993年 | 16篇 |
1992年 | 36篇 |
1991年 | 40篇 |
1990年 | 29篇 |
1989年 | 33篇 |
1988年 | 25篇 |
1987年 | 13篇 |
1986年 | 17篇 |
1985年 | 17篇 |
1984年 | 28篇 |
1983年 | 17篇 |
1982年 | 9篇 |
1981年 | 10篇 |
1980年 | 17篇 |
1979年 | 11篇 |
1978年 | 8篇 |
1977年 | 9篇 |
1976年 | 5篇 |
1975年 | 6篇 |
1974年 | 7篇 |
排序方式: 共有5076条查询结果,搜索用时 15 毫秒
101.
J L Wiggs G R Howell K Linkroum W Abdrabou E Hodges C E Braine L R Pasquale G J Hannon J L Haines S W M John 《Clinical genetics》2013,84(2):167-174
Primary open angle glaucoma (POAG) is a genetically and phenotypically complex disease that is a leading cause of blindness worldwide. Previously we completed a genome‐wide scan for early‐onset POAG that identified a locus on 9q22 (GLC1J). To identify potential causative variants underlying GLC1J, we used targeted DNA capture followed by high throughput sequencing of individuals from four GLC1J pedigrees, followed by Sanger sequencing to screen candidate variants in additional pedigrees. A mutation likely to cause early‐onset glaucoma was not identified, however COL15A1 variants were found in the youngest affected members of 7 of 15 pedigrees with variable disease onset. In addition, the most common COL15A1 variant, R163H, influenced the age of onset in adult POAG cases. RNA in situ hybridization of mouse eyes shows that Col15a1 is expressed in the multiple ocular structures including ciliary body, astrocytes of the optic nerve and cells in the ganglion cell layer. Sanger sequencing of COL18A1, a related multiplexin collagen, identified a rare variant, A1381T, in members of three additional pedigrees with early‐onset disease. These results suggest genetic variation in COL15A1 and COL18A1 can modify the age of onset of both early and late onset POAG. 相似文献
102.
Roberta Roncarati Chiara Viviani Anselmi Peter Krawitz Giovanna Lattanzi Yskert von Kodolitsch Andreas Perrot Elisa di Pasquale Laura Papa Paola Portararo Marta Columbaro Alberto Forni Giuseppe Faggian Gianluigi Condorelli Peter N Robinson 《European journal of human genetics : EJHG》2013,21(10):1105-1111
Familial dilated cardiomyopathy (DCM) is a heterogeneous disease; although 30 disease genes have been discovered, they explain only no more than half of all cases; in addition, the causes of intra-familial variability in DCM have remained largely unknown. In this study, we exploited the use of whole-exome sequencing (WES) to investigate the causes of clinical variability in an extended family with 14 affected subjects, four of whom showed particular severe manifestations of cardiomyopathy requiring heart transplantation in early adulthood. This analysis, followed by confirmative conventional sequencing, identified the mutation p.K219T in the lamin A/C gene in all 14 affected patients. An additional variant in the gene for titin, p.L4855F, was identified in the severely affected patients. The age for heart transplantation was substantially less for LMNA:p.K219T/TTN:p.L4855F double heterozygotes than that for LMNA:p.K219T single heterozygotes. Myocardial specimens of doubly heterozygote individuals showed increased nuclear length, sarcomeric disorganization, and myonuclear clustering compared with samples from single heterozygotes. In conclusion, our results show that WES can be used for the identification of causal and modifier variants in families with variable manifestations of DCM. In addition, they not only indicate that LMNA and TTN mutational status may be useful in this family for risk stratification in individuals at risk for DCM but also suggest titin as a modifier for DCM. 相似文献
103.
Elena Sommariva Carlo Pappone Filippo Martinelli Boneschi Chiara Di Resta Maria Rosaria Carbone Erika Salvi Pasquale Vergara Simone Sala Daniele Cusi Maurizio Ferrari Sara Benedetti 《European journal of human genetics : EJHG》2013,21(9):911-917
Brugada syndrome is an inherited arrhythmogenic disorder leading to sudden death predominantly in the 3–4 decade. To date the only reliable treatment is the implantation of a cardioverter defibrillator; however, better criteria for risk stratification are needed, especially for asymptomatic subjects. Brugada syndrome genetic bases have been only partially understood, accounting for <30% of patients, and have been poorly correlated with prognosis, preventing inclusion of genetic data in current guidelines. We designed an observational study to identify genetic markers for risk stratification of Brugada patients by exploratory statistical analysis. The presence of genetic variants, identified by SCN5A gene analysis and genotyping of 73 candidate polymorphisms, was correlated with the occurrence of major arrhythmic events in a cohort of 92 Brugada patients by allelic association and survival analysis. In all, 18 mutations were identified in the SCN5A gene, including 5 novel, and statistical analysis indicated that mutation carriers had a significantly increased risk of major arrhythmic events (P=0.024). In addition, we established association of five polymorphisms with major arrhythmic events occurrence and consequently elaborated a pilot risk stratification algorithm by calculating a weighted genetic risk score, including the associated polymorphisms and the presence of SCN5A mutation as function of their odds ratio. This study correlates for the first time the presence of genetic variants with increased arrhythmic risk in Brugada patients, representing a first step towards the design of a new risk stratification model. 相似文献
104.
105.
106.
Dario Leosco Valentina Parisi Teresa Pellegrino Gennaro Pagano Grazia Daniela Femminella Agnese Bevilacqua Stefania Paolillo Roberto Formisano Gaetana Ferro Claudio de Lucia Maria Prastaro Pasquale Perrone Filardi Alberto Cuocolo Giuseppe Rengo Nicola Ferrara 《European journal of nuclear medicine and molecular imaging》2015,42(10):1601-1611
107.
Tao Huang Yan Zheng Qibin Qi Min Xu Sylvia H. Ley Yanping Li Jae H. Kang Janey Wiggs Louis R. Pasquale Andrew T. Chan Eric B. Rimm David J. Hunter JoAnn E. Manson Walter C. Willett Frank B. Hu Lu Qi 《Diabetes》2015,64(9):3146-3154
The first epigenome-wide association study of BMI identified DNA methylation at an HIF3A locus associated with BMI. We tested the hypothesis that DNA methylation variants are associated with BMI according to intake of B vitamins. In two large cohorts, we found significant interactions between the DNA methylation–associated HIF3A single nucleotide polymorphism (SNP) rs3826795 and intake of B vitamins on 10-year changes in BMI. The association between rs3826795 and BMI changes consistently increased across the tertiles of total vitamin B2 and B12 intake (all P for interaction <0.01). The differences in the BMI changes per increment of minor allele were −0.10 (SE 0.06), −0.01 (SE 0.06), and 0.12 (SE 0.07) within subgroups defined by increasing tertiles of total vitamin B2 intake and −0.10 (SE 0.06), −0.01 (SE 0.06), and 0.10 (SE 0.07) within subgroups defined by increasing tertiles of total vitamin B12 intake. In two independent cohorts, a DNA methylation variant in HIF3A was associated with BMI changes through interactions with total or supplemental vitamin B2, vitamin B12, and folate. These findings suggest a potential causal relation between DNA methylation and adiposity. 相似文献
108.
109.
110.
The protease inhibitor ritonavir inhibits the functional activity of the multidrug resistance related-protein 1 (MRP-1) 总被引:4,自引:0,他引:4
BACKGROUND: Efflux pumps situated on the plasma membrane, such as P-glycoprotein (Pgp) and the multidrug resistance related-protein 1 (MRP-1), have been shown to extrude HIV protease inhibitors from the cell. MRP-1 is present on many barrier sites throughout the body, such as the blood-brain and blood-testis interfaces and could reduce the concentration of protease inhibitors in these sanctuary sites for HIV-1 replication. Factors that modulate efflux pump function in vivo are poorly defined. OBJECTIVE: To analyze the inhibitory potential of the anti-retroviral drugs indinavir, amprenavir, ritonavir, lamivudine or zidovudine to modulate MRP-1 function. METHODS: Effect of anti-HIV drugs on the efflux pump activity of MRP-1 was evaluated in the presence of increasing concentrations of human plasma, using UMCC-1/VP cells which stably over-express MRP-1. MRP-1 activity was abrogated by probenecid. The potential of blocking MRP-1 function for an extended (3 day) time period, was also examined in MRP-1 over-expressing cells cultured with either probenecid or the anti-retroviral drugs and a cytotoxic compound (etoposide) that is transported by MRP-1. RESULTS: Ritonavir inhibited the functional activity of MRP-1 similarly to probenecid, as demonstrated by re-sensitization of MRP-1 over-expressing cells to cytotoxic effects of etoposide. Inhibition by ritonavir was inversely related to the concentration of human plasma added to the cells (r2 = 0.89). Other anti-HIV drugs didn't affect the MRP-1 mediated efflux of etoposide. CONCLUSIONS: These data may be exploitable to further improve sanctuary site concentrations of anti-HIV or anti-cancer drugs by using ritonavir as a lead compound to develop more potent MRP-1 inhibitors. 相似文献