全文获取类型
收费全文 | 224篇 |
免费 | 22篇 |
国内免费 | 8篇 |
专业分类
儿科学 | 3篇 |
妇产科学 | 7篇 |
基础医学 | 25篇 |
口腔科学 | 1篇 |
临床医学 | 44篇 |
内科学 | 37篇 |
皮肤病学 | 1篇 |
神经病学 | 14篇 |
特种医学 | 1篇 |
外科学 | 14篇 |
综合类 | 26篇 |
预防医学 | 17篇 |
眼科学 | 2篇 |
药学 | 58篇 |
中国医学 | 3篇 |
肿瘤学 | 1篇 |
出版年
2022年 | 1篇 |
2021年 | 3篇 |
2020年 | 3篇 |
2019年 | 10篇 |
2018年 | 9篇 |
2017年 | 10篇 |
2016年 | 12篇 |
2015年 | 10篇 |
2014年 | 11篇 |
2013年 | 24篇 |
2012年 | 16篇 |
2011年 | 22篇 |
2010年 | 18篇 |
2009年 | 15篇 |
2008年 | 10篇 |
2007年 | 20篇 |
2006年 | 9篇 |
2005年 | 8篇 |
2004年 | 11篇 |
2003年 | 5篇 |
2002年 | 13篇 |
2001年 | 4篇 |
2000年 | 4篇 |
1991年 | 1篇 |
1986年 | 4篇 |
1985年 | 1篇 |
排序方式: 共有254条查询结果,搜索用时 15 毫秒
1.
目的:建立一种简单、稳定、可靠的PON1基因多态性分析法。方法:取外周静脉血100μl,用ROSE法提取基因组DNA,用两对引物:P192F 5′-TAT TGT TGC TGT GGG ACC TGA G-3′,P192R 5′-CAC GCT AAA CCC AAA TAC ATC TC-3′;P55F 5′-GAA GAG TGA TGT ATA GCC CCA G-3′,P55R 5′-TTT AAT CCA GAG CTA ATG AAA GCC-3分别进行PCR扩增,用限制性内切酶AlwI,NlaⅢ对两种PCR产物分别进行酶切,3%琼脂糖凝胶电泳。结果:扩增的两个PCR产物在192、55多态性位点大小分别为99bp、170bp。Alw I酶切后,凝胶电脉得到完全酶切(66bp,33bp),部分酶切(99bp、66bp、33bp),未被酶切(99bp)三种类型DNA片段(RR,QR,QQ基因型);NlaⅢ酶切后,凝胶电脉得到部分酶切(170bp,126bp,44bp),未被酶切(170bp)两种类型DNA片段(LM,LL基因型)。经双盲重复检测,结果一致。应用此方法对胃癌患者血样标本检测,发现其PON1基因多态性在192位点频率较高。结论:采用一步PCR-RFLP技术可以建立简单、稳定、可靠的PON1基因多态性分析法。 相似文献
2.
One hundred and sixty-three healthy Chinese subjects of both sexes were studied for serum paraoxonase (PON) polymorphism, and levels of lipids and apolipoproteins in order to examine effects of PON alleles on these parameters. The level of serum triglyceride was significantly higher in high activity allele (PON*B) compared with that in low activity allele (PON*A) in both sexes (P less than 0.01). The subjects with PON A had significantly higher LDL cholesterol (P less than 0.05) and lower Apo A-II and ApoB levels. The influence of serum paraoxonase on serum lipids was estimated further by Spearman's rank correlation. In the males, there was a significant negative correlation of serum paraoxonase activity with total (P less than 0.05) and LDL (P less than 0.01) cholesterol levels, and positive correlation with HDL cholesterol and Apo A-II levels (P less than 0.05). Serum paraoxonase activity had a high positive correlation with serum triglyceride levels in both sexes (P less than 0.001). Serum ApoB level had a positive correlation with the enzyme activity only in females (P less than 0.01). The allelic effect of PON on these parameters was studied by multiple regression analysis. The high activity allele (PON*B) was associated with higher serum triglyceride level (P less than 0.001) and ApoB (P less than 0.001), while it had lowering influence on total cholesterol (P less than 0.05) and LDL cholesterol (P less than 0.005) in men. The average allelic effect of PON was found to be about 22% for serum triglycerides, 11% for LDL cholesterol, 14% for Apo A-II and 19% for Apo B in the present study. This study suggests a possible significant role of serum paraoxonase alleles in the metabolism of serum lipids and apolipoproteins. 相似文献
3.
4.
5.
目的研究国人血清对氧磷酶1(PON1)基因192位Gln/Arg多态性对冠心病患者血管内皮功能的影响。方法应用聚合酶链式反应-限制性片断长度多态性(PCR-RFLP)方法,对石家庄地区汉族151例冠心病患者及91例正常对照者PON1基因192位Gln/Arg多态性进行分析,同时应用超声检测肱动脉内皮功能。结果冠心病组及正常对照组PON1基因均以QR基因型为主,其频率分别为48%和54%。冠心病组RR型基因频率高于对照组(P<0.05)。平衡法计算等位基因的频率,R等位基因在冠心病组明显增高(65%vs39%,P<0.05)。冠心病组PON1各基因型内皮依赖性舒张功能均低于对照组(P<0.05),以RR基因型最为明显,其次为QR基因性;而两组非内皮依赖性舒张功能差异无显著性。结论PON1基因192位Gln/Arg多态性可能与冠心病患者血管内皮功能异常有关。R等位基因可能为血管内皮功能受损的相对危险因素,且参与冠心病的发病。 相似文献
6.
Mohd Wamique Wahid Ali D. Himanshu Reddy Preeti Vishwakarma Mohd Waseem 《Diabetes & Metabolic Syndrome: Clinical Research & Reviews》2018,12(6):843-847
Aim
To evaluate the serum paraoxonase 1 activity and determine its association with duration in type 2 Diabetes mellitus patients.Methods
A total of 80 cases from type 2 diabetes mellitus and healthy controls were enrolled in the present case control study. Human serum PON1 concentration was measured by ELISA and western blotting and it activity was determined spectrophotometrically using 4-nitrophenyle acetate. Diagnostic accuracy of serum PON1 to identify type 2 Diabetes mellitus was calculated with ROC analysis.Result
Serum concentration of LDL, VLDL, TG, A1C, FBS and TC levels showed significantly higher levels in type 2 diabetes patients as compared to healthy controls, however there were no significant differences found in the level of HDL. Serum PON1 concentration and activity monitored in patients with >1?year diabetes showed higher level (75.1?±?6.8?ng/mL) as compared to patients with >3?years diabetes (65.24?±?1.6?ng/mL), its level was further decreased in patients with >5 (53.8?±?2.6?ng/mL) and >7?years (48.1?±?2.7?ng/mL) of diabetes. PON1 concentration decreased as the duration of diabetes increased. PON1 level was further decreased due to habits like smoking and alcohol consumption.Conclusion
Serum PON1 levels decrease in states of high oxidative stress like metabolic syndrome, obesity, uncontrolled diabetes, and dyslipidemia. It can be used as diagnostic marker for diabetes mellitus along with increased TG, LDL, VLDL and FBG. 相似文献7.
Mohamed F. Abdel Rahman Ingy M. Hashad Khaled Abou-Aisha Sahar M. Abdel-Maksoud Mohamed Z. Gad 《Archives of Medical Science》2015,11(3):513-520
Introduction
The enzyme paraoxonase-1 (PON1) represents an endogenous defense mechanism against vascular oxidative stress, thereby contributing to the prevention of atherosclerosis. Several polymorphisms have been reported in the PON1 gene, including Q192R. PON1 phenotype is commonly expressed as the paraoxonase/arylesterase ratio (PON/ARE). The major aim of this study was to investigate the association between PON1 Q192R polymorphism, PON1 phenotypes and the incidence of early-onset acute myocardial infarction (AMI) in Egyptians.Material and methods
The study subjects consisted of 102 AMI patients and 72 age-matched healthy controls. Genotyping and enzyme activities were determined using PCR-RFLP and kinetic spectrophotometric assays, respectively.Results
The genotype distribution for the PON1 gene was significantly different between AMI patients (QQ = 38.24%, QR = 49.02%, RR = 12.75%) and controls (QQ = 66.67%, QR = 25%, RR = 8.33%). Allele frequencies were also significantly different between patients (Q = 62.75%, R = 37.25%) and controls (Q = 79.17%, R = 20.83%). The genotypes QR and RR showed higher risk for AMI compared to the homozygous QQ (odds ratio (OR) = 3.231, p < 0.001). The average PON/ARE ratio in MI patients (1.187 ±0.1) did not differ significantly from controls (1.118 ±0.26). However, it showed a significant difference among different genotypes in both AMI patients (QQ = 0.91 ±0.11, QR = 1.09 ±0.11 and RR = 2.65 ±0.4) (p = 0.0002) and controls (QQ = 0.68 ±0.1, QR = 1.07 ±0.11 and RR = 4.89 ±2.84) (p < 0.0001).Conclusions
PON1 192R allele represents an independent risk factor for early-onset AMI in Egyptians, and PON1 Q192R polymorphism modulates the paraoxonase phenotype. 相似文献8.
Mustafa Gullulu Serdar Kahvecioglu Melahat Dirican Ibrahim Akdag Nihal Ocak Celalettin Demircan 《Renal failure》2013,35(4):433-439
Background. Cardiovascular disease is the most common cause of morbidity and mortality in patients with chronic renal failure. Glomerulonephritic patients have an increased risk for cardiovascular disease, but its etiology is unclear. It is known that an increase in oxidizability of apolipoprotein B-containing lipoproteins has a key role in the initiation of atherosclerosis, and paraoxonase enzyme activity particularly has a preventive role against atherosclerosis. The aim of the present study was to evaluate the oxidizability of apolipoprotein B-containing lipoproteins, serum, and urinary paraoxonase/arylesterase activities in glomerulonephritis patients who had normal lipid parameters and creatinine levels. Methods. Thirty-two patients with glomerulonephritis and 22 healthy controls were included in this study. A total of 32 patients (including nine with membranous GN, eight with immunoglobulin A nephropathy, eight with mesangial proliferative GN, five with focal-segmental glomerulosclerosis, one with diffuse proliferative GN, and one with minimal chance disease having biopsy proven GN) were enrolled into the study. We compared serum and urinary paraoxonase, arylesterase, serum lipids, urea, creatinine, hemoglobin, total protein and albumin values between groups. Results. Serum urea, creatinine, total protein, albumin, uric acid, hemoglobin, and lipid parameters were similar in the glomerulonephritis and control groups (p > 0.05). PON1 activity was significantly lower in GN group than controls, but there was no statistically significant difference on arylesterase activity between groups. Oxidizability of apolipoprotein B-containing lipoproteins was significantly higher in GN group than controls. Conclusion. Our study shows that the findings of normal serum levels of creatinine, lipids, and proteins increased the oxidizability of apolipoprotein B-containing lipoproteins, and any decrease in PON1 activity in patients diagnosed with GN should be considered important. Hence, the immediate commencement of preventive as well as curative treatment in other to avoid the risk of cardiovascular and renal problems would be a correct approach. 相似文献
9.
Tiziana Bacchetti Simona Masciangelo Tatiana Armeni Virginia Bicchiega Gianna Ferretti 《Metabolism: clinical and experimental》2014
Objective
Methylglyoxal (MG), a reactive carbonyl compound formed primarily from triose phosphates, appears to be involved in the molecular mechanisms of diabetes, end-stage renal disease and neurodegenerative diseases. Methylglyoxal exerts several biological activities. Among these it promotes advanced glycation end products (AGEs), which are crucial in pathogenesis of human disease. Previous studies have demonstrated that MG reacts with proteins and compositional modifications reflect loss of biological activity. The aim of the study was to investigate the effect of in vitro MG-induced glycation on human high density lipoprotein (HDL) and on the activity of the enzyme paraoxonase-1 (PON1).Methods
HDL was incubated in the absence or in the presence of MG (0.2 mmol/L and 1.0 mmol/L) (MG-HDL) for different times (3, 6, 24 h) at 37 ° C. We evaluated apoprotein compositional changes, in both control and MG treated HDL, using intrinsic fluorescence of tryptophan and monitoring the decrease of free amino groups. Furthermore we evaluated fluorescent advanced glycation end products (Ex = 370 nm, Em = 440 nm) and the activity of HDL-paraoxonase.Results
We demonstrated that human HDL is susceptible to glycation by MG (0.2 mmol/L and 1 mmol/L). The decrease of free amino groups and of intrinsic fluorescence of tryptophan demonstrates HDL apoprotein modifications in HDL incubated with MG. The compositional changes are associated with a significant increase in fluorescent advanced glycation end products and with a significant decrease of paraoxonase-1 enzyme activity associated with the HDL surface.Conclusions
HDL-associated paraoxonase is responsible for the anti-inflammatory and anti-oxidative properties of HDL and detoxification against homocysteine-thiolactone. Therefore, modifications of apoprotein composition and the decrease of paraoxonase-1 activity in MG-treated HDL could affect the protective effect exerted by HDL against oxidative damage and could contribute to complications in patients affected by diseases associated with aging and oxidative stress. 相似文献10.
目的探讨对氧磷酶(PON1)的基因多态性对接触有机磷的作业工人血清对氧磷酶(sPON)活力的影响。方法采用标准曲线法测定作业工人和对照者sPON活力,PCR-限制性片段长度多态性分析PON1基因192位点的基因型。结果合并敌敌畏和对硫磷暴露组后,不同基因型sPON活力均值为195.0(谷氨酸纯合子,Gln/Gln)、304.6(谷氨酸/精氨酸杂合子,Gln/Arg)和368.4(精氨酸纯合子,Arg/Arg),呈Gln/Gln→Gln/Arg→Arg/Arg递增的趋势,并且差异有统计学意义(P=0.03)。结论PON1基因192位点的多态性影响sPON的活力,可能调节个体对甲基对硫磷的毒性的易感性。 相似文献