全文获取类型
收费全文 | 999篇 |
免费 | 65篇 |
国内免费 | 44篇 |
专业分类
1108篇 |
出版年
2023年 | 21篇 |
2022年 | 46篇 |
2021年 | 43篇 |
2020年 | 17篇 |
2019年 | 20篇 |
2018年 | 19篇 |
2017年 | 20篇 |
2016年 | 16篇 |
2015年 | 22篇 |
2014年 | 38篇 |
2013年 | 71篇 |
2012年 | 29篇 |
2011年 | 29篇 |
2010年 | 35篇 |
2009年 | 36篇 |
2008年 | 38篇 |
2007年 | 44篇 |
2006年 | 55篇 |
2005年 | 43篇 |
2004年 | 36篇 |
2003年 | 45篇 |
2002年 | 32篇 |
2001年 | 27篇 |
2000年 | 26篇 |
1999年 | 14篇 |
1998年 | 24篇 |
1997年 | 20篇 |
1996年 | 11篇 |
1995年 | 12篇 |
1994年 | 9篇 |
1993年 | 7篇 |
1992年 | 15篇 |
1991年 | 9篇 |
1990年 | 11篇 |
1989年 | 14篇 |
1988年 | 7篇 |
1987年 | 4篇 |
1986年 | 6篇 |
1985年 | 17篇 |
1984年 | 18篇 |
1983年 | 8篇 |
1982年 | 15篇 |
1981年 | 14篇 |
1980年 | 9篇 |
1979年 | 14篇 |
1978年 | 11篇 |
1977年 | 11篇 |
1976年 | 11篇 |
1974年 | 3篇 |
1973年 | 3篇 |
排序方式: 共有1108条查询结果,搜索用时 0 毫秒
11.
The malaria parasite, Plasmodium falciparum, enhances the rate and extent of sickling of infected hemoglobin S heterozygous human erythrocytes. Upon sickling of the host cell, the parasite is killed. Parasite-free lysates of highly infected cells were analyzed to determine the mechanism by which sickling is enhanced. The intraerythrocytic pH of the infected cell was estimated to be 0.4 units below that of the uninfected cell, a difference which could result in a 20-fold increase in the extent of sickling under physiological conditions. Sickle-cell hemoglobin (HbS) heterozygous (AS) erythrocytes had decreased intracellular potassium after 24 hr of culture under conditions which cause sickling and parasite death. When infected AS cells were cultured in high-potassium medium under these conditions the parasites were protected. The medium did not prevent sickling but did maintain normal intracellular potassium levels. It is suggested that sequestration of trophozoite-infected AS cells in the venules leads to the sickling of the host cell, loss of erythrocytic potassium, and parasite death. The resulting attenuation of parasite multiplication would favor the survival of the HbS heterozygote and maintain the HbS gene at high frequencies in areas endemic for falciparum malaria. 相似文献
12.
13.
Raitis Peculis Ilze Konrade Elina Skapare Davids Fridmanis Liene Nikitina-Zake Aivars Lejnieks Valdis Pirags Maija Dambrova Janis Klovins 《Gene》2013
The glyoxalase system and its main enzyme, glyoxalase 1 (GLO1), protect cells from advanced glycation end products (AGEs), such as methylglyoxal (MG) and other reactive dicarbonyls, the formation of which is increased in diabetes patients as a result of excessive glycolysis. MG is partly responsible for harmful protein alterations in living cells, notably in neurons, leading to their dysfunction, and recent studies have shown a negative correlation between GLO1 expression and tissue damage. Neuronal dysfunction is a common diabetes complication due to elevated blood sugar levels, leading to high levels of AGEs. The aim of our study was to determine whether single nucleotide polymorphisms (SNPs) in the GLO1 gene influence activity of the enzyme. In total, 125 healthy controls, 101 type 1 diabetes, and 100 type 2 diabetes patients were genotyped for three common SNPs, rs2736654 (A111E), rs1130534 (G124G), and rs1049346 (5′-UTR), in GLO1. GLO1 activity was determined in whole blood lysates for all participants of the study. 相似文献
14.
Background and aims
Sustained interaction of advanced glycation end products (AGEs) with their receptor RAGE and subsequent signaling plays an important role in the development of diabetic complications. Genetic variation of RAGE gene may be associated with the development of vascular complications in type 2 diabetes mellitus (T2DM).Objectives
The present study aimed to explore the possible association of RAGE gene polymorphisms namely − 374T/A, − 429T/C and G82S with serum level of AGEs, paraoxonase (PON1) activity and macro-vascular complications (MVC) in Indian type 2 diabetes mellitus patients (T2DM).Methods
A total of 265 diabetic patients, including DM without any complications (n = 135), DM-MVC (n = 130) and 171 healthy individuals were enrolled. Genotyping of RAGE variants were assessed by polymerase chain reaction-restriction fragment length polymorphism. Serum AGEs were estimated by ELISA and fluorometrically. and PON1 activity was assessed spectrophotometrically.Results
Of the three examined SNPs, association of − 429T/C polymorphism with MVC in T2DM was observed (OR = 3.001, p = 0.001) in the dominant model. Allele ‘A’ of − 374T/A polymorphism seems to confer better cardiac outcome in T2DM. Patients carrying C allele (− 429T/C) and S allele (G82S) had significantly higher AGEs levels. − 429T/C polymorphism was also found to be associated with low PON1 activity. Interaction analysis revealed that the risk of development of MVC was higher in T2DM patients carrying both a CC genotype of − 429T/C polymorphism and a higher level of AGEs (OR = 1.343, p = 0.040).Conclusion
RAGE gene polymorphism has a significant effect on AGEs level and PON1 activity in diabetic subjects compared to healthy individuals. Diabetic patients with a CC genotype of − 429T/C are prone to develop MVC, more so if AGEs levels are high and PON1 activity is low. 相似文献15.
Marijana Popović Hadžija Marina Korolija Nikolina Jemin Iva Pavković Pajica Pavković Edita Pape Medvidović Mirko Hadžija 《Gene》2013
Genetic variants of IL-18 and IL-12B may be important in immunoregulatory abnormalities, observed in the patients with Type 1 diabetes mellitus (T1DM), that contribute to individual differences in response to a treatment. Therefore, we examined the significance of IL-18-137G/C, IL-18-607C/A, and IL-12B A/C polymorphisms in Croatians (187 patients, 236 controls), not only as factors that contribute to susceptibility to T1DM, but also as determinants of the clinical presentation of disease. 相似文献
16.
E. Lendaro R. Ippoliti A. Brancaccio A. Bellelli B. Vallone G. Ivaldi G.V. Sciarratta C. Castello S. Tomova M. Brunori G. Amiconi 《生物化学与生物物理学报:疾病的分子基础》1992,1180(1):15-20
Hemoglobin Dallas, an α-chain variant with a substitution of lysine for asparagine at position 97(G4), was found to have increased oxygen affinity () and reduced Bohr effect (about 50%). Addition of allosteric effectors (such as 2,3-diphosphoglycerate, inositol hexakisphosphate and bezafibrate) led to a decrease in oxygen affinity and increase in cooperative energy. Kinetic studies at pH 7.0 and 20°C revealed that (i), the overall rate of oxygen dissociation is 1.4-fold slower than that for HbA and (ii), the carbon monoxide dissociation rate is unaffected. The abnormal properties of this hemoglobin variant can be atttributed to a more ‘relaxed’ T-state. 相似文献
17.
We have used [2-13C]d-glucose and carbon-13 nuclear magnetic resonance (NMR) spectroscopy to investigate metabolic fluxes through the major pathways of glucose metabolism in intact human erythrocytes and to determine the interactions among these pathways under conditions that perturb metabolism. Using the method described, we have been able to measure fluxes through the pentose phosphate pathway, phosphofructokinase, the 2,3-diphosphoglycerate bypass, and phosphoglycerate kinase, as well as glucose uptake, concurrently and in a single experiment. We have measured these fluxes in normal human erythrocytes under the following conditions: (1) fully oxygenated; (2) treated with methylene blue; and (3) deoxygenated. This method makes it possible to monitor various metabolic effects of stresses in normal and pathological states. Not only has 13C-NMR spectroscopy proved to be a useful method for measuring in vivo flux through the pentose phosphate pathway, but it has also provided additional information about the cycling of metabolites through the non-oxidative portion of the pentose phosphate pathway. Our evidence from experiments with [1-13C]-, [2-13C]-, and [3-13C]d-glucoses indicates that there is an observable reverse flux of fructose 6-phosphate through the reactions catalyzed by transketolase and transaldolase, even in the presence of a net flux through the pentose phosphate pathway. 相似文献
18.
以血红蛋白和乙肝表面抗原(HBsAg)为模型,联用双偏振光干涉分析仪(DPI)和原子力显微镜(AFM)研究在固-液界面上的吸附行为.结果发现:当溶液环境中血红蛋白的质量浓度为1.08 mg/mL时,测得在硅羟基表面吸附的平均厚度为3.54 nm,蛋白颗粒直径达60~ 150 nm,远高于血红蛋白的分子尺寸,说明血红蛋白在固-液界面上发生团聚.当HBsAg质量浓度为0.67 mg/mL时,测得在硅羟基表面及DEAE琼脂糖表面吸附的平均厚度分别为1.06和23.69 nm,表面吸附的蛋白颗粒直径分别为288~401和520 ~ 971 nm,是单分子HBsAg尺寸的13.1~44.1倍,表明在模型蛋白表面都形成了大的团聚体. 相似文献
19.