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11.
Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in treating diabetes, heart ischemia, and cancer 总被引:2,自引:2,他引:0
The fraction of pyruvate dehydrogenase complex (PDC) in the active form is reduced by the activities of dedicated PD kinase
isozymes (PDK1, PDK2, PDK3 and PDK4). Via binding to the inner lipoyl domain (L2) of the dihydrolipoyl acetyltransferase (E2
60mer), PDK rapidly access their E2-bound PD substrate. The E2-enhanced activity of the widely distributed PDK2 is limited
by dissociation of ADP from its C-terminal catalytic domain, and this is further slowed by pyruvate binding to the N-terminal
regulatory (R) domain. Via the reverse of the PDC reaction, NADH and acetyl-CoA reductively acetylate lipoyl group of L2,
which binds to the R domain and stimulates PDK2 activity by speeding up ADP dissociation. Activation of PDC by synthetic PDK
inhibitors binding at the pyruvate or lipoyl binding sites decreased damage during heart ischemia and lowered blood glucose
in insulin-resistant animals. PDC activation also triggers apoptosis in cancer cells that selectively convert glucose to lactate.
Received 25 August 2006; received after revision 20 November 2006; accepted 20 December 2006 相似文献
12.
From endoderm to pancreas: a multistep journey 总被引:2,自引:0,他引:2
Spagnoli FM 《Cellular and molecular life sciences : CMLS》2007,64(18):2378-2390
The formation of the vertebrate pancreas is a complex process that typifies the basic steps of embryonic development. It involves the establishment of competence, specification, signaling from neighboring tissues, morphogenesis, and the elaboration of tissue-specific genetic networks. A full analysis of this multistep process will help us to understand classic principles of embryonic development. Furthermore, this will provide the blueprint for experimental programming of pancreas formation from embryonic stem cells in the context of diabetes cell-therapy. Although in the past decade many studies have contributed to a solid foundation for understanding pancreatogenesis, important gaps persist in our knowledge of early pancreas formation. This review will summarize the current understanding of the early mechanisms coming into play to pattern the "pre-pancreatic" region within the endoderm and, gradually, specify the pancreatic tissue. 相似文献
13.
目的 探讨孕早期睡眠时长和午睡频次对妊娠糖尿病(GDM)的影响.方法 采用病例对照研究设计,选取2018年4月至2019年5月在安徽省妇幼保健院、吉安市妇幼保健院产检的孕妇作为研究对象.通过问卷调查收集研究对象的睡眠和午睡等信息,GDM的诊断来自孕中期常规口服葡萄糖耐量试验结果.结果 共纳入500名研究对象,其中病例组... 相似文献
14.
G. M. C. Janssen P. Schwertman T. A. T. Wanga R. S. Jahangir Tafrechi P. J. A. van den Broek A. K. Raap 《Cellular and molecular life sciences : CMLS》2009,66(4):721-730
Cytoplasmic translation is under sophisticated control but how cells adapt its rate to constitutive loss of mitochondrial
oxidative phosphorylation is unknown. Here we show that translation is repressed in cells with the pathogenic A3243G mtDNA
mutation or in mtDNA-less ρ0 cells by at least two distinct pathways, one transiently targeting elongation factor eEF-2 and the other initiation factor
eIF-2α constitutively. Under conditions of exponential cell growth and mammalian target of rapamycin (mTOR) activation, eEF-2
becomes transiently phosphorylated by an AMP-activated protein kinase (AMPK)-dependent pathway, especially high in mutant
cells. Independent of AMPK and mTOR, eIF-2α is constitutively phosphorylated in mutant cells, likely a signature of endoplasmic
reticulum (ER)-stress response induced by the loss of oxidative phosphorylation. While the AMPK/eEF-2K/eEF-2 pathway appears
to function in adaptation to physiological fluctuations in ATP levels in the mutant cells, the ER stress signified by constitutive
protein synthesis inhibition through eIF-2α-mediated repression of translation initiation may have pathobiochemical consequences.
Received 29 October 2008; received after revision 11 December 2008; accepted 16 December 2008 相似文献
15.
N. Asano 《Cellular and molecular life sciences : CMLS》2009,66(9):1479-1492
A large number of compounds mimicking the structures of monosaccharides or oligosaccharides have been discovered from natural
sources. Such sugar mimics inhibit carbohydrate-degrading enzymes because of a structural resemblance to the sugar moiety
of the natural substrate. Carbohydrate-degrading enzymes are involved in a wide range of important biological processes, such
as intestinal digestion, posttranslational processing of the sugar chain of glycoproteins, their quality control mechanisms,
lysosomal catabolism of glycoconjugates, and some viral infections. It has now been realized that inhibitors of the enzymes
have enormous therapeutic potential in diabetes and lysosomal storage disorders. In this review, the general bioactivity,
current applications, and the prospects for new therapeutic applications are described.
Received 27 August 2008; received after revision 08 November 2008; accepted 03 December 2008 相似文献
16.
3-甲基-1-(2-(1-哌啶基)苯基)丁胺的合成 总被引:1,自引:1,他引:0
分别以2-氯苯腈和2-氟苯甲醛为原料, 采用两种路线合成3-甲基-1-(2-(1-哌啶基)苯基)丁胺, 总收率分别为42%和31%. 关键中间体及最终化合物的结构经质谱、 核磁共振氢谱及碳谱得到确证. 相似文献
17.
Liver X receptors in cardiovascular and metabolic disease 总被引:5,自引:0,他引:5
Liver X receptors (LXRs) α and β are nuclear oxysterol receptors and metabolic sensors initially found to regulate cholesterol
metabolism and lipid biosynthesis. Recent studies have elucidated the importance of LXR in the development of cardiovascular
diseases and metabolic disorders. LXR agonists prevent development of atherosclerosis by modulation of metabolic as well as
inflammatory gene expression in rodent models. Moreover, LXR activation inhibits hepatic gluconeogenesis and lowers serum
glucose levels, indicating possible application of LXR activation in the treatment of diabetes mellitus. However, first-generation
LXR agonists elevate hepatic and serum trigylceride levels, making subtype-specific agonists and selective LXR modulators
rather than unselective LXR agonists a potential pharmacological strategy. This review summarizes the multiple physiological
and pathophysiological implications of LXRs and observations that identify LXRs as potential targets for therapeutic interventions
in human cardiovascular and metabolic disease.
Received 30 August 2005; received after revision 10 October 2005; accepted 4 November 2005 相似文献
18.
Lifei Liu Jingjing Lei Haiyun Liu Qinjie Zou Yuhua Sun Yancheng Xu Huimin Bi Fengjiao Deng Xueling Shao Siyang Liu 《武汉大学学报:自然科学英文版》2010,15(2):171-175
In this study, we selected 10 susceptible SNPs loci to investigate their contribution to susceptibility to type 2 diabetes in Han Chinese among Hubei population. We genotyped SNPs rs5219, rs1801282, rs1470579, rs1111875, rs1081661, rs7754840, rs4506565, rs13266634, rs4402960, and rs5643981 by using the method of polymerase chain reaction-ligase detection reaction (PCR-LDR). In a case-control study, we have genotyped the 10 candidate susceptibility SNP loci, and here, we reported that the SNP rs5219 in KCNJ1... 相似文献
19.
《河南师范大学学报(自然科学版)》2013,(6):122-126
目的:探讨运动干预、二甲双胍及其两者联合治疗对于新诊断2型糖尿病患者治疗效果的差异.方法:60例新诊断2型糖尿病患者,将其随机分为3组,根据所入组别对其进行运动干预、二甲双胍治疗及其联合治疗12周,比较各组治疗前后多项指标的变化情况及疗效的差异.结果:12周后各组患者的BMI,FBG及2hOGTT,HbA1c,INS,TC,TG,LDL-C较治疗前均明显下降(P<0.05),而HDL-C较治疗前明显增加(P<0.05).二甲双胍组与运动干预组比较,治疗后FBG,2hOGTT,HbA1c,INS差异无统计学意义,而运动干预组患者BMI,TC,TG,LDL-C的下降程度及HDL-C的升高程度明显高于二甲双胍组;运动干预联合二甲双胍组治疗后BMI,FBG,2hOGTT,HbA1c,INS,TC,TG、LDL-C下降程度及HDL-C的升高程度均明显高于二甲双胍组及运动干预组(P<0.05).结论:单纯运动干预与二甲双胍治疗对于初发2型糖尿病患者的血糖及胰岛功能的控制疗效相仿,强化运动治疗能明显改善患者的体质及血脂,而二甲双胍联合运动干预对于初诊2型糖尿病患者的血糖、血脂、胰岛功能及体质有明显改善. 相似文献
20.
本文对Ⅱ型糖尿病患者的血清唾液酸进行了检测,结果发现Ⅱ型糖尿病人的血清唾液酸浓度增高,阳性率为71.1%,与正常人及炎症病人比较均有极显著性差异(P<0.001),但结果低于恶性肿瘤病人,糖尿病人的病情与血清唾液酸浓度成正相关。结果表明,糖尿病与血清唾液酸有着相互关系。 相似文献