全文获取类型
收费全文 | 748篇 |
免费 | 56篇 |
国内免费 | 45篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 20篇 |
妇产科学 | 24篇 |
基础医学 | 187篇 |
口腔科学 | 13篇 |
临床医学 | 29篇 |
内科学 | 185篇 |
皮肤病学 | 6篇 |
神经病学 | 69篇 |
特种医学 | 9篇 |
外科学 | 36篇 |
综合类 | 63篇 |
预防医学 | 58篇 |
眼科学 | 2篇 |
药学 | 44篇 |
中国医学 | 1篇 |
肿瘤学 | 100篇 |
出版年
2023年 | 4篇 |
2022年 | 8篇 |
2021年 | 17篇 |
2020年 | 20篇 |
2019年 | 20篇 |
2018年 | 15篇 |
2017年 | 34篇 |
2016年 | 29篇 |
2015年 | 28篇 |
2014年 | 64篇 |
2013年 | 75篇 |
2012年 | 51篇 |
2011年 | 59篇 |
2010年 | 45篇 |
2009年 | 58篇 |
2008年 | 77篇 |
2007年 | 63篇 |
2006年 | 53篇 |
2005年 | 34篇 |
2004年 | 26篇 |
2003年 | 19篇 |
2002年 | 7篇 |
2001年 | 10篇 |
2000年 | 4篇 |
1999年 | 6篇 |
1997年 | 3篇 |
1996年 | 4篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1986年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有849条查询结果,搜索用时 15 毫秒
841.
Krivak TC Darcy KM Tian C Bookman M Gallion H Ambrosone CB Deloia JA 《Gynecologic oncology》2011,122(1):121-126
Objective
This study evaluated common polymorphisms in excision repair cross-complementation group 1 (ERCC1) involved in repair of platinum-induced DNA damage in advanced-stage, epithelial ovarian/peritoneal/tubal cancer (EOC/PPC/FTC) patients treated with intravenous carboplatin- and paclitaxel-based chemotherapy.Methods
Pyrosequencing was performed to examine single nucleotide polymorphisms (SNPs) in codon 118 and C8092A in ERCC1 in leukocyte DNA from the Gynecologic Oncology Group phase III protocol, GOG-182. Kaplan-Meier method and adjusted Cox regression modeling were used to examine associations between ERCC1 polymorphisms and progression-free survival (PFS) and overall survival (OS).Results
The genotype distribution at codon 118 (n = 278) in ERCC1 for CC, CT, and TT was 23%, 45% and 32%, and the median OS was 32, 47 and 43 months, respectively. Patients with the CT + TT versus CC genotype in codon 118 in ERCC1 were at a reduced risk of death (hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.49-0.95, p = 0.025). The genotype distribution for C8092A in ERCC1 (N = 280) was 50%, 42% and 8%, and the median OS was 45, 40 or 30 months for CC, CA and AA, respectively. Women with the CA + AA versus CC genotype in C8092A in ERCC1 had a trend suggesting an increased risk of death (HR = 1.29, 95% CI = 0.97-1.72, p = 0.077).Conclusions
The polymorphism in codon 118 in the DNA repair gene ERCC1 was an independent predictor for better survival in EOC/PPC/FTC patients treated with intravenous carboplatin- and paclitaxel-based chemotherapy. The relationship between the C8092A polymorphisms in ERCC1 and survival was modest with an effect size that was not always statistically significant. 相似文献842.
Słopien R Jasniewicz K Meczekalski B Warenik-Szymankiewicz A Lianeri M Jagodziński PP 《Maturitas》2008,61(3):252-255
Objective
Disturbances in the folate-dependent one-carbon metabolism have been reported in depression. Polymorphic variants of genes encoding key enzymes of folate and methionine metabolism may have an impact on catecholamine catabolism conducted by catechol-O-methyltransferase.Methods
The distribution of polymorphisms of genes encoding methylenetetrahydrofolate reductase (MTHFR); methionine synthase (MTR); 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase (MTHFD1) was examined in postmenopausal women with (n = 83) and without depression (n = 89).Results
We found a significant contribution of the MTHFR 677C > T polymorphic variants to depression in postmenopausal women. Odds ratio (OR) for women with depression and MTHFR TT genotype was 3.478 (95% CI = 1.377–8.783), P = 0.0096 and OR of the TT and CT genotypes was 2.345 (95% CI = 1.258–4.373), P = 0.0086. Moreover, after stratification based on depression severity in postmenopausal women, we found that the MTHFR TT genotype displayed a 4.831-fold increased risk of moderate and severe depression (95% CI = 1.975–11.820, P = 0.0008). We did not observe statistical differences in the distribution of MTR 2756A > G and MTHFD1 1958G > A polymorphic variants in groups of postmenopausal women with and without depression. However, the MTR GG genotype exhibited a 5.750-fold increased risk of moderate and severe depression in postmenopausal women (95% CI = 1.547–21.379, P = 0.013).Conclusions
Our findings indicate a significant role of folate and possible methionine metabolism involvement in the development of depression in postmenopausal women. 相似文献843.
Huntington disease mutation in Venezuela: age of onset,haplotype analyses and geographic aggregation
The aggregation of patients with Huntington's disease (HD) around Lake Maracaibo, Zulia State, Venezuela, is widely recognized,
but the epidemiology of HD in the whole country is relatively unstudied. We have examined 279 individuals from 60 unrelated
affected families residing in various areas of Venezuela for the presence of CAG repeats and other features associated with
HD. The number of expanded repeats in 139 carriers varied from 35 to 112. Based on our examination of 71 symptomatic individuals,
we developed a log-transformed regression equation, y = −0.0238x + 2.6616, to enable the prediction of age of onset in asymptomatic carriers. Intragenic haplotypes were constructed with
two VNTRs (variable number of tandem repeats) and two SNPs (single nucleotide polymorphisms) in the promoter region as well
as CCG repeat and Δ2642 polymorphisms to assess kinship between families. In 43 of 45 tested families, the haplotype on the
mutated chromosome was 1;G;C;7;(A). The other haplotypes observed, 1;G;C;7;(B) and 4;G;C;7;(A), were of Peruvian and French
origins, respectively. The geographic source of the first affected ancestor was assessed in 54 families from 15 different
states. Residents of the states of Miranda, Lara and Táchira, excluding those of Zulia, had a mutated allele prevalence five-
to ninefold higher than that of other areas. A low (approx. 1/200,000) prevalence, a wide-spread distribution with aggregation
in some states and a likely remote European Caucasoid origin are defining epidemiologic features of HD in Venezuela.
An erratum to this article can be found at 相似文献
844.
Suwannakul S Ieiri I Kimura M Kawabata K Kusuhara H Hirota T Irie S Sugiyama Y Higuchi S 《Journal of human genetics》2008,53(10):899-904
The impact of SLCO1B1 polymorphism on the pharmacokinetics of olmesartan and on the pharmacokinetic interaction between pravastatin and olmesartan
was investigated. On day 1, ten healthy volunteers took an oral dose (10 mg) of pravastatin. After a 3-day washout period,
each subject received olmesartan medoxomil (10 mg) for 3 days. On day 8, they received olmesartan medoxomil (10 mg) and pravastatin
(10 mg) concurrently, and pharmacokinetic profiles were compared with those in each single-dose phase with regard to the SLCO1B1 genotypes (*1b/*1b, *1b/*15, and *15/*15). In the single-dose phase, the mean C
max and AUC0–24 of olmesartan tended to be higher in *15/*15 subjects than in *1b/*1b subjects, while the mean CL
t
/F (±SD) in *15/*15 subjects was significantly lower than that in *1b/*1b subjects. No statistically significant differences
were observed in any pharmacokinetic parameters between single-dose and co-administration phases for both pravastatin and
RMS-416. These results suggest that OATP1B1 plays a role in the pharmacokinetics of olmesartan, and the co-administration
of olmesartan does not affect the pharmacokinetics of pravastatin or its metabolite, RMS-416, although larger scale clinical
studies are needed to confirm these observations due to the small sample size in the present study. 相似文献
845.
Giacconi R Caruso C Malavolta M Lio D Balistreri CR Scola L Candore G Muti E Mocchegiani E 《Ageing research reviews》2008,7(4):306-318
Inflammation and genetics are prominent mechanisms in the pathogenesis of atherosclerosis (AT) and its complications. In this review we discuss the possible impact on AT development of several genetic determinants involved in inflammation, oxidative stress and cytoprotection (IL-6, TNF-α, IL-10, CD14, TLR4, MT, HSP70). Genetic polymorphisms of these genes may affect a differential inflammatory response predisposing to AT. However, allelic polymorphisms of genes which increase the risk of AT frequently occur in the general population but, only adequate gene-environment-polymorphism interactions promote the onset of the disease. Zinc deficiency has been suggested as an environmental risk factor for AT. With advancing age, the incidence of zinc deficiency increases for several reasons. Among them, dietary intake, malabsorption and genetic background of inflammatory markers may be involved. A crucial contribution may also be played by increased oxidative stress which may lead to the appearance of dysfunctional proteins, including metallothioneins (MT) that are in turn involved in zinc homeostasis. The detection of candidate genes related to inflammation and promoting AT and their reciprocal influence/interaction with zinc status might allow earlier appropriate dietary interventions in genetically susceptible subjects. 相似文献
846.
目的 探讨中国广东汉族人血HLA-A、-B、-C、-DRB1、-DQB1等位基因与HBV感染罹患肝细胞癌(HCC)的关联性。方法 采用聚合酶链反应-直接测序分型法检测广东地区56例HCC患者和97例健康志愿者血HLA-A、-B、-C、-DRB1、-DQB1基因型。结果 HCC患者血HLA- A*02:03和A*02:07等位基因频率明显高于健康人(0.116071对0.046392和0.178571对0.061856,x2=5.167、x2=10.33,P=0.023、P=0.001);HCC患者血HLA-B*46:01等位基因频率为0.205357,明显高于健康人的0.108247(x2=5.439,P=0.02);HCC患者血HLA- DRB1*14:54 和 DRB1*12:02等位基因频率明显高于健康人(0.089286对0和0.142857对0.06701,x2=14.502、x2=4.761,P=0.000、P=0.026);HCC患者血HLA-DQB1*05:03等位基因频率为0.098214,明显高于健康人的0.036082(x2=4.951,P=0.026);HCC患者血HLA-A*30:01等位基因频率为0.017857,明显低于健康人的0.082474(x2=5.355,P=0.021);HCC患者血HLA-B*13:02等位基因频率为0.008929,明显低于健康人的0.07732(x2=6.702,P=0.01)。结论 在中国广东地区人群中,HLA-A*02:03、A*02:07、HLA-B*46:01、HLA-DRB1*14:54、DRB1*12:02、HLA-DQB1*05:03与感染HBV的HCC发病有关,而与HLA-A*30:01和HLA-B*13:02可能无关。 相似文献
847.
The Contribution of Vitamin D Receptor Gene Polymorphisms in Osteoporosis and Familial Osteoporosis 总被引:5,自引:0,他引:5
L. Fountas P. Moutsatsou I. Kastanias N. Tamouridis M. Tzanela M. Anapliotou C. E. Sekeris 《Osteoporosis international》1999,10(5):392-398
It is well established that genetic factors play a major role in the pathogenesis of osteoporosis. Previous reports have
suggested that vitamin D receptor (VDR) gene polymorphisms, particularly the BB, tt and AA genotypes, are associated with
low bone mineral density (BMD). If these VDR genotypes are indeed an important determinant of BMD, then a population of related
osteoporotic individuals (mother–daughter or sister–sister relationship) should have a high prevalence of the BB, tt or AA
VDR genotypes. To test this hypothesis we determined the VDR genotypes in 26 osteoporotic persons (age 44.3 ± 12.7 years,
mean ± SD) belonging to 12 families. Furthermore, for comparison with existing studies, we applied the VDR genotype analysis
in a population of 53 unrelated healthy subjects (age 45.2 ± 9.8 years, mean ± SD) and 59 unrelated osteoporotic subjects
(age 52.1 ± 9.0 years, mean ± SD). The menopausal status of the healthy and osteoporotic populations was pre-, peri- and mostly
early postmenopausal. The proportions of the three genotypes, BB, tt and AA, within the 12 osteoporotic families were 15%,
12% and 27%, respectively, whereas the proportions of the other three homozygous genotypes (bb, TT, aa) were 50%, 50% and
23%. The distribution of the BB, tt and AA genotypes in the normal population was 21%, 21% and 36%, respectively (vs bb, TT,
aa: 36%, 38%, 21%), whereas in the osteoporotic population it was 24%, 20% and 34% (vs bb, TT, aa: 27%, 34%, 14%). Our data
indicate that there is not a statistically significant (p>0.05) difference in the VDR genotype frequencies within osteoporotic families as compared with the same genotypes in the
population of unrelated normal or osteoporotic subjects. VDR genotype analysis showed no significant relation between VDR
polymorphisms and BMD or Z-score values at the lumbar spine. This study demonstrates the lack of a heritability pattern between the BB, tt and AA genotypes
and low BMD.
Received: 29 October 1998 / Accepted: 19 April 1999 相似文献
848.
目的新近的研究提示CD40/CD40L信号途径对急性冠状动脉综合征的发病及预后均具有一定影响。本研究旨在探讨CD40L G基因单核苷酸多态性与急性冠状动脉综合征患者冠状动脉病变程度间的关系。方法搜集2008年8月至2010年8月间在北京安贞医院抢救中心确诊为急性冠状动脉综合征的患者共482例,总结分析其临床特征、相关危险因素及血清单核细胞和血小板表达CD40水平以及CD40L G基因单核苷酸多态性对冠状动脉病变程度的影响。结果 (1)6.8%(n=33)的急性冠状动脉综合征患者未检测到血清sCD40L(<95 ng/L),449例患者平均血清sCD40L为296±25 ng/L,sCD40L平均水平男性为309 ng/L,女性为195 ng/L,男性高于女性(P<0.001),sCD40L水平随着冠状动脉病变程度加重而升高(P<0.001)。(2)不同基因型间血清sCD40L水平与冠状动脉评分存在显著性差异(P<0.001),趋势具有统计学意义。其中以GG基因型的sCD40L水平最高,为409ng/L,冠状动脉病变程度最严重(P<0.001)。(3)多因素分析显示,在矫正年龄、性别及高血脂、高血压、糖尿病等危险因素后,CD40L G基因多态性与冠状动脉病变程度密切相关,它们的OR值分别为1.00、1.32、3.41(P≤0.001)。结论急性冠状动脉综合征患者血清sCD40L水平及CD40L G基因多态性与冠状动脉病变程度密切相关,在急性冠状动脉综合征临床危险分层中,血清sCD40L水平及CD40L G基因多态性是一个不容忽视的方面。 相似文献
849.
《Human immunology》2023,84(2):80-88
Human Mannose-binding lectin (MBL) is a protein encoded by MBL2 gene involved in the activation of the lectin-complement pathway. Several studies emphasized the role of MBL2 gene in several infectious diseases’ susceptibility, including HIV-1 infection. We aim to investigate the impact of 10 MBL2 gene polymorphisms located in the promoter, 5′UTR and exon 1 regions on HIV-1 physiopathology. The polymorphisms genotyping of 400 individuals, which 200 were HIV-1 positive patients and 200 were controls, was performed by PCR-sequencing. Our results showed that rs503037 and rs1800451 polymorphisms are associated with a high risk of HIV-1 infection susceptibility while rs7096206 and rs11003123 showed a protective effect. A significant association between haplotype CGA and HIV-1 infection susceptibility was also found in the exon 1 region. Moreover, rs11003124, rs7084554, rs36014597 and rs11003123 polymorphisms revealed an association with treatment response outcome as measured by RNA viral load. This study highlights the importance of MBL2 polymorphisms in the modulation of HIV-1 infection susceptibility and the contribution to treatment response outcomes among Moroccan subjects. 相似文献