首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   530篇
  免费   23篇
  国内免费   1篇
  2022年   2篇
  2021年   6篇
  2020年   3篇
  2018年   5篇
  2017年   6篇
  2016年   9篇
  2015年   13篇
  2014年   24篇
  2013年   37篇
  2012年   32篇
  2011年   34篇
  2010年   23篇
  2009年   14篇
  2008年   32篇
  2007年   38篇
  2006年   30篇
  2005年   30篇
  2004年   30篇
  2003年   42篇
  2002年   30篇
  2001年   9篇
  2000年   10篇
  1999年   8篇
  1998年   7篇
  1997年   6篇
  1996年   3篇
  1995年   5篇
  1994年   4篇
  1993年   2篇
  1992年   4篇
  1991年   5篇
  1990年   3篇
  1989年   7篇
  1988年   2篇
  1987年   5篇
  1986年   6篇
  1985年   4篇
  1984年   6篇
  1983年   1篇
  1982年   2篇
  1981年   1篇
  1980年   1篇
  1979年   2篇
  1976年   1篇
  1975年   1篇
  1974年   4篇
  1973年   1篇
  1972年   1篇
  1971年   1篇
  1963年   1篇
排序方式: 共有554条查询结果,搜索用时 31 毫秒
171.
Methylglyoxal (MG), a physiological &#102 -dicarbonyl compound is derived from glycolytic intermediates and produced during the Maillard reaction. The Maillard reaction, a non-enzymatic reaction of ketones and aldehydes with amino group of proteins, contributes to the aging of proteins and to complications associated with diabetes. In our previous studies (Che, et al. (1997) "Selective induction of heparin-binding epidermal growth factor-like growth factor by MG and 3-deoxyglucosone in rat aortic smooth muscle cells. The involvement of reactive oxygen species formation and a possible implication for atherogenesis in diabetes". J. Biol. Chem., 272 , 18453-18459), we reported that MG elevates intracellular peroxide levels, but the mechanisms for this remain unclear. Here, we report that MG inactivates bovine glutathione peroxidase (GPx), a major antioxidant enzyme, in a dose- and time-dependent manner. The use of BIAM labeling, it was showed that the selenocysteine residue in the active site was intact when GPx was incubated with MG. MALDI-TOF-MS (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry) and protein sequencing examined the possibility that MG modifies arginine residues in GPx. The results show that Arg 184 and Arg 185, located in the glutathione binding site of GPx was irreversively modified by treatment with MG. Reactive dicarbonyl compounds such as 3-deoxyglucosone, glyoxal and phenylglyoxal also inactivated GPx, although the rates for this inactivation varied widely. These data suggest that dicarbonyl compounds are able to directly inactivate GPx, resulting in an increase in intracellular peroxides which are responsible for oxidative cellular damage.  相似文献   
172.
Isobe  Shiho  Ota  Ayaka  Takata  Shiori  Hamajima  Rina  Makino  Shizuka  Kobayashi  Jun  Kobayashi  Michihiro  Ikeda  Motoko 《Cytotechnology》2021,73(4):643-655
Cytotechnology - The cell line NISES-AnPe-428 (AnPe), derived from the Chinese oak silkworm Antheraea pernyi, was characterized for its permissiveness and productivity for six different...  相似文献   
173.
Mitochondria are considered to play an important role in oxidative stress response since they are a source of reactive oxygen species and are also targeted by these species. This study examined the mitochondrial conditions in cells of epithelial origin that were exposed to H(2)O(2) and found a decline in the membrane potential along with a specific loss of UQCRC1, a sub-unit of complex III, suggesting that mitochondrial dysfunction occurs upon exposure to oxidative stress. This observation led to the hypothesis that certain cellular responses to oxidative stress occurred because of mitochondrial dysfunction. When mitochondria-less (pseudo ρ0) cells were examined as a model of mitochondrial dysfunction, striking similarities were found in their cellular responses compared with those found in cells exposed to oxidative stress, including changes in gene expression and gelatinolytic enzyme activities, thus suggesting that cellular responses to oxidative stress were partly mediated by mitochondrial dysfunction. This possibility was further validated by microarray analysis, which suggested that almost one-fourth of the cellular responses to oxidative stress were mediated by mitochondrial dysfunction that accompanies oxidative stress, thereby warranting a therapeutic strategy that targets mitochondria for the treatment of oxidative stress-associated diseases.  相似文献   
174.
Highlights? WNK4 kinase is a substrate of KLHL3-Cullin3-targeted ubiquitination ? PHAII-causing mutations of WNK4, KLHL3, and Cullin3 decrease WNK4 ubiquitination ? Impaired WNK4 ubiquitination activates the OSR1/SPAK-NCC axis and causes hypertension  相似文献   
175.

Background/Objective

Gene-gene interactions in the reverse cholesterol transport system for high-density lipoprotein-cholesterol (HDL-C) are poorly understood. The present study observed gene-gene combination effect and interactions between single nucleotide polymorphisms (SNPs) in ABCA1, APOA1, SR-B1, and CETP in serum HDL-C from a cross-sectional study in the Japanese population.

Methods

The study population comprised 1,535 men and 1,515 women aged 35–69 years who were enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. We selected 13 SNPs in the ABCA1, APOA1, CETP, and SR-B1 genes in the reverse cholesterol transport system. The effects of genetic and environmental factors were assessed using general linear and logistic regression models after adjusting for age, sex, and region.

Principal Findings

Alcohol consumption and daily activity were positively associated with HDL-C levels, whereas smoking had a negative relationship. The T allele of CETP, rs3764261, was correlated with higher HDL-C levels and had the highest coefficient (2.93 mg/dL/allele) among the 13 SNPs, which was statistically significant after applying the Bonferroni correction (p<0.001). Gene-gene combination analysis revealed that CETP rs3764261 was associated with high HDL-C levels with any combination of SNPs from ABCA1, APOA1, and SR-B1, although no gene-gene interaction was apparent. An increasing trend for serum HDL-C was also observed with an increasing number of alleles (p<0.001).

Conclusions

The present study identified a multiplier effect from a polymorphism in CETP with ABCA1, APOA1, and SR-B1, as well as a dose-dependence according to the number of alleles present.  相似文献   
176.
A crude enzyme preparation hydrolyzing konjac mannan was extracted from germinating konjac tubers, and purified by chromatography with DEAE-cellulose and alkali-swollen cellulose, and by gel-filtration on Sephadex G-100. The purified enzyme preparation showed optimal activity at pH 4.7, optimum temperature at 40°C. It was considerably stable at pH’s between 4.0 and 8.0, but inactivated rapidly by temperaters above 50°C. Hydrolysis of the mannan by this enzyme proceeded by typical random mechanism, and the rate was in agreement with an empirical equation, p=0.43 E0.77 to0.5. As the Km and Vmax values for mannan, 7.14×10-2(%)and 23.8×10-3 (ΔOD500nm) were obtained, respectively.  相似文献   
177.
(±)-Tricarbonyl(η5-1-formyl-2-methylcyclopentadienyl)manganese (1) was optically resolved with horse liver alcohol dehydrogenase (HLADH) and two species of yeasts, Saccharomyces sp. H-1 and Rhodotorula rubra IFO 889. Usually, (1R)-1 was preferentially reduced to give (?)-alcohol 2 of ≥ 97% e.e. ? 84% e.e. Ketone analogue (±)-tricarbonyl(η5-1-acetyl-2-methylcyclopentadienyl)-manganese (4) was reduced by the yeasts. The major product by S. sp. H-1 was the (1S,2R,1′S)-(+)-alcohol (5) (≥ 98% e.e.) and the minor product, the (1R,2S,1′S)-(?)-alcohol (6) (86% e.e.). R. rubra gave only the latter alcohol (≥ 99 % e.e.). The Stereodifferentiation mechanism for these bioreductions is discussed in terms of the Prelog rule. The mechanism for HLADH reduction was examined with computer graphics.  相似文献   
178.
We have investigated the immunomodulatory mechanisms of Bifidobacterium pseudocatenulatum JCM7041 (Bp) as model of probiotics following oral administration to mice. This study was conducted with the aim of clarifying the mechanism of immunomodulation induced by oral administration of probiotic bacteria through elucidation of the detailed mechanism of transfer of orally administered bacterial cells within the body and the interaction between bacterial cells and cells of the immune tissues. We observed the localization of Bp in mice following oral administration, showing that Bp was surrounded by CD11c+ cells in Peyer’s patches (PP) and cecal patches (CP). These results indicated that Bp might induce CD11c+ cell-mediated immune responses directly. Furthermore, IL-10 and IL-12p40 production by Thy1.2 cells, including CD11c+ cells, increased significantly. Production of IL-10 and IL-12p40 by bone marrow-derived dendritic cells (BMDC) was significantly increased by Bp stimulation. These results suggest that oral administration of Bp induces immune responses directly following capture by CD11c+ dendritic cells (DCs). Subsequently, we observed oral administration of Bp for 1 week induced IgA and IgA-associated cytokine production by CP and PP cells, suggesting that Bp induced DC-mediated immune responses on CP as well as PP.  相似文献   
179.
Involvement of impaired peritoneal immunosurveillance systems has been well established in the pathology of endometriosis. On the other hand, it has been observed that peritoneal administration of IL-12 suppress development of endometriotic lesions in a mouse endometriosis model. We investigated the effect of peritoneal administration of IL-12 on the peritoneal immunosurveillance system regarding NK cells in the mouse model. Treating the endometrial-tissue challenged mice with IL-12 for 5 consecutive days, from day -2 to day 2 (implantation of the endometrial tissues was done on day 0), cytotoxicity of splenic NK cells was enhanced immediately after the administration, on day 3, and development of the endometriotic lesions was reduced on day 21. In vivo NK cell depletion by administration of anti-IL-2Rβ mAb resulted in reduction of the cytotoxicity of splenic NK cells concomitant with a significant attenuation of suppressive effect of IL-12 on development of endometriotic lesions. Therefore, it was suggested that IL-12 suppresses development of endometriotic lesions via activation of NK cells, and that NK cells are involved in the primary defense for the development of endometriotic lesions.  相似文献   
180.
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号