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
61.
Ying-Zi Liu Bei-Sha Tang Xin-Xiang Yan Jie Liu Dong-Sheng Ouyang Li-Nuo Nie Lan Fan Zhi Li Wei Ji Dong-Li Hu Dan Wang Hong-Hao Zhou 《European journal of clinical pharmacology》2009,65(7):679-683
Objective To evaluate the impact of the DRD2 TaqIA and DRD3 Ser9Gly polymorphisms on the efficacy of pramipexole in treating patients
with Parkinson’s disease (PD).
Methods Thirty patients with PD prospectively received pramipexole 0.25 mg three times daily for 2 months. Unified Parkinson Disease
Rating Scale (UPDRS) assessments were conducted at baseline and 2 months after treatment initiation. Improvement by 20% or
more in the total score on the UPDRS was considered to indicate responsiveness. The PCR–restriction fragment length polymorphism
analysis was used to analyze the DRD2 Taq1A and DRD3 Ser9Gly genotype.
Results The DRD2 Taq1A allele frequencies were A141.7 (A1) and 58.3% (A2), and the DRD3 Ser9Gly allele frequencies were 68.3 (Ser)
and 31.7% (Gly). When the subjects were grouped by the DRD3 Ser9Gly polymorphism, the response rates for pramipexole treatment
were significantly higher in the Ser/Ser group (60%) than in the group containing the Gly allele (13%). There was a significant
association between the DRD3 Ser9Gly polymorphism and response rate to pramipexole in PD patients (P = 0.024). When the subjects were grouped by the DRD2 Taq1A polymorphism, there were no significant differences among the
three Taq1A genotypes.
Conclusions DRD3 Ser9Gly polymorphisms are significantly associated with the therapeutic efficacy of pramipexole in Chinese patients with
PD. A large-scale and multi-dose group study in patients with PD is necessary for evaluating the impact of the genetic polymorphisms
of the dopamine receptor on the therapeutic effects of pramipexole. 相似文献
62.
In recent years, few fields in medicine have witnessed discoveries as momentous as those pertaining to the liver. Dramatic advances have been made, particularly in the areas of molecular biology and genetics. A joint EASL/AASLD Monothematic Conference was held on June 23rd-24th, 2006, in Modena, Italy, to bring the latest breakthroughs in different fields of genetics to hepatologists. This article reports the highlights of the conference and summarizes the main conclusions and implications for clinical and experimental hepatology. 相似文献
63.
64.
The ability to predict the risk of MEN2 and medullary thyroid carcinoma (MTC) by genetic RET proto-oncogene analysis has provided an essential tool in identifying patients in whom thyroid cancer can be prevented by prophylactic thyroidectomy but emphasizes the need for clear policy guidelines. Children of families with RET cysteine mutations (exons 10, 11, 13, and 16) may develop early metastatic tumours and require prophylactic thyroidectomy. The 918 mutation associated with MEN2B is associated with early aggressive behaviour and distant metastatic spread. This has led to active screening of affected families underlining the need for specific intervention strategies.
Aim
To evaluate the risk to children of families with MEN2 and to assess the risk and determine the treatment.Methods
Twenty-five patients from 10 families with MEN2 phenotypes were screened for RET mutations. Polymerase chain reaction amplification was performed on all 21 exons of the RET proto-oncogene, followed by heteroduplex single-strand conformation polymorphism (HEX-SSCP) analysis. Polymerase chain reaction products demonstrating variation in the HEX-SSCP gels were subjected to automated DNA sequencing analysis.Results
Eleven significant RET mutations were detected in affected families. Eight index cases received initial thyroidectomy for established MTC (plus 2 advised). In the family members screened, 3 prophylactic thyroidectomies (2 with early MTC) were performed and a further 2 recommended. An exon 10 C620W missense mutation (the “Janus” gene) was detected in a patient with Hirschsprung's disease plus 1 family member.Conclusion
RET analysis of MEN has revolutionized the management of children of families with MEN2 and allowed surgical prediction and prophylaxis to take place. The presence of an exon 10 C620W mutation in association with Hirschsprung's disease was difficult to assess. We suggest possible guidelines for management of families with MTC and the role of genetic testing in their evaluation. 相似文献65.
66.
María A. García-Gonzlez María A. Prez Aísa Mark Strunk Rafael Benito Elena Piazuelo Pilar Jimnez Federico Sopea Angel Lanas 《Human immunology》2009,70(11):935-945
We aimed to evaluate the influence of Helicobacter pylori infection and IL-1/TNF gene polymorphisms on interleukin (IL)-1β and tumor necrosis factor (TNF)-α gastric mucosal production. IL-1β and TNF-α levels in homogenized biopsy specimens taken from the antrum and corpus of 81 patients were measured by enzyme-linked immunosorbent assay. Genomic DNA was typed for the IL1B-511, IL1B+3954, variable number of tandem repeat (VNTR) IL1RN, TNFA-308, TNFA-238, LTA NcoI, and LTA Bsi gene polymorphisms by polymerase chain reaction, restriction fragment length polymorphism, and TaqMan assays. H. pylori infection and CagA/VacA antibody status were determined by Western blot. IL-1β and TNF-α protein levels were significantly higher in the gastric antrum of patients infected with H. pylori compared with uninfected patients [9.54 (5.07–16.28) vs. 4.55 (3.69–8.28) pg IL-1β/mg protein, p = 0.004, and 1.5 (0.7–2.71) vs. 0.63 (0.3–1.26) pg TNF-α/mg protein, p = 0.001]. Among H. pylori-infected individuals, carriers of the IL1RN*2 allele had significantly higher antrum mucosal IL-1β levels than noncarriers [15.97 (9.59–26.6) vs. 10.08 (7.72–13.33), p = 0.008]. No association between gastric mucosal TNF-α levels and genotypes of the TNFA and LTA gene polymorphisms was reported. Our results indicate that the VNTR polymorphism of the IL1RN gene influences IL-1β gastric mucosal production in patients infected with H. pylori. 相似文献
67.
Christie Cluett 《Mechanisms of ageing and development》2009,130(9):553-563
Avoiding age-related disease until late in life is key to ‘successful’ ageing. Over 300 genome-wide association study papers have been published. Over 50 variants have already been identified as associated with four key age-related diseases, namely cardiovascular disease, type 2 diabetes, osteoporosis and prostate cancer. We review these findings with reference to pathways linked to ageing, including cell cycle control or cell senescence, oxidative stress, insulin, IGF1 and other endocrine signalling, and inflammation.Many variants are disease specific or of unknown function. Of the remainder, those with functions likely to be relevant to ageing are predominantly in cell cycle control and therefore tissue repair. Three loci associated with two or more age-related diseases have been identified, two apparently related to cell cycle control. The third shared locus (near TERT), may be involved in telomerase activity and is associated with several environmentally caused age-related cancers.These findings challenge current ideas, suggesting large numbers of cell type specific effects, often driven by regulatory rather than coding changes. They also confirm the central role of cell cycle and re-growth as a key pathway underlying the human variation in successful ageing. 相似文献
68.
Cheng J Liu J Li X Yu L Peng J Zhang R Geng Y Nie S 《Clinica chimica acta; international journal of clinical chemistry》2008,392(1-2):46-51
BACKGROUND: Nitric oxide (NO) synthesized by endothelial nitric oxide synthase (eNOS) plays a key role in vascular regulation and atherosclerosis, therefore, eNOS may be a candidate gene for ischemic stroke (IS). However, it is still controversial whether eNOS polymorphisms are a risk factor for IS. METHODS: Three polymorphisms of the eNOS gene (-922A/G, -786T/C, 894G/T) were determined by using TaqMan SNP genotyping assay in 309 Chinese patients with IS and 309 Chinese controls. RESULTS: The frequency of eNOS -922 G allele was significantly higher in the patients than the controls (12.14% vs 8.09%, P=0.018). The distribution of eNOS genotypes differed insignificantly between the 2 groups. The frequency of the eNOS -786 CC genotype was higher in the patients than the controls (OR=3.819, P=0.029). With respect to -922A/G, the AG+GG genotype increased the risk for IS (OR=1.523, P=0.047). After adjustment for confounding factors, the odds ratios of -786 CC and -922 variant genotype (AG+GG) for IS were 4.580 and 1.656, respectively. However, haplotype analysis revealed the frequencies of Hap4 (GCG) and Hap7 (GCT) were significantly higher in the patients than the controls (P=0.035, 0.042). CONCLUSIONS: eNOS -922A/G and -786T/C may affect the susceptibility to IS and certain haplotypes of the eNOS gene may be associated with a higher susceptibility to IS. 相似文献
69.
目的 研究醛固酮合酶基因(CYP11B2)和11-β羟化酶基因(CYP11B1)多态性与原发性醛同酮增多症(PA)发病风险之间的相关性.方法 对醛固酮瘤(APA)和特发性醛崮酮增多症(IHA)患者(APA 134例,IHA 45例)及正常人群(118名)中CYP11B2和CYP1181基因的5个多态性位点进行检测.其中,intron 2采用2个独立的PCR反应,其余位点均采用Taqman探针法.采用Haploview 4.0、SNPassoc 1.5-3和Haplo.stats 1.3.8软件分析CYPllB2和CYP1181基因多态性与PA的关系.结果 所选位点均获成功检测,APA和IHA组中rs6410位点的A等位基因频数显著高于对照组(P=1.09×10-5,P=0.015).与对照组相比,APA组中rs6410位点AA基因型和AG基因型比例增高(P=2.19×10-4),而IHA组中rs6410位点AA基因型和AG基因型仅在年龄、性别和体质量指数校对后比例增高(OR=4.06,95%CJ 1.31~12.66;OR=2.41,95%CI 1.02~5.72).APA组中发现1个易感单体型AAAWT(OR=1.44,95%CI 1.19~1.76),IHA组中发现3个易感单体型AAAWT、AGGWT和AGAWC(OR=1.55,95%CI 1.23~1.96;OR=1.49,95%CI 1.17~1.89;OR:1.40,95%CI 1.04~1.88).同时在APA组中发现1个保护性单体型GGAWT(OR:0.73,95%CI 0.55~0.97).结论 CYP11B2和CYP11B1基因多态性与APA和IHA的发病显著相关. 相似文献
70.
Fatemi SH King DP Reutiman TJ Folsom TD Laurence JA Lee S Fan YT Paciga SA Conti M Menniti FS 《Schizophrenia Research》2008,101(1-3):36-49
Schizophrenia has a complex genetic underpinning and variations in a number of candidate genes have been identified that confer risk of developing the disorder. We report in the present studies that several single nucleotide polymorphisms (SNPs) and a two-SNP haplotype in PDE4B are associated with an increased incidence of schizophrenia in two large populations of Caucasian and African American patients. The SNPs in PDE4B associated with schizophrenia occur in intronic sequences in the vicinity of a critical splice junction that gives rise to the expression of PDE4B isoforms with distinct regulation and function. We also observed specific decreases in phosphodiesterase 4B (PDE4B) isoforms in brain tissue obtained postmortem from patients diagnosed with schizophrenia and bipolar disorder. PDE4B metabolically inactivates the second messenger cAMP to regulate intracellular signaling in neurons throughout the brain. Thus, the present observations suggest that dysregulation of intracellular signaling mediated by PDE4B is a significant factor in the cause and expression, respectively, of schizophrenia and bipolar disorder and that targeting PDE4B-regulated signaling pathways may yield new therapies to treat the totality of these disorders. 相似文献