全文获取类型
收费全文 | 447篇 |
免费 | 32篇 |
出版年
2022年 | 4篇 |
2021年 | 14篇 |
2020年 | 7篇 |
2019年 | 5篇 |
2018年 | 8篇 |
2017年 | 7篇 |
2016年 | 10篇 |
2015年 | 25篇 |
2014年 | 25篇 |
2013年 | 28篇 |
2012年 | 27篇 |
2011年 | 28篇 |
2010年 | 19篇 |
2009年 | 18篇 |
2008年 | 19篇 |
2007年 | 12篇 |
2006年 | 28篇 |
2005年 | 21篇 |
2004年 | 11篇 |
2003年 | 20篇 |
2002年 | 15篇 |
2001年 | 9篇 |
2000年 | 15篇 |
1999年 | 12篇 |
1998年 | 6篇 |
1997年 | 5篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1992年 | 11篇 |
1991年 | 5篇 |
1990年 | 5篇 |
1989年 | 5篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 7篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1979年 | 4篇 |
1978年 | 1篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1966年 | 1篇 |
排序方式: 共有479条查询结果,搜索用时 15 毫秒
81.
Marta Cruces-Sande Rocío Vila-Bedmar Alba C. Arcones Águeda González-Rodríguez Patricia Rada Virginia Gutiérrez-de-Juan Javier Vargas-Castrillón Paula Iruzubieta Cristina Sánchez-González Laura Formentini Javier Crespo Carmelo García-Monzón María L. Martínez-Chantar Ángela M. Valverde Federico Mayor Cristina Murga 《生物化学与生物物理学报:疾病的分子基础》2018,1864(12):3655-3667
Insulin resistance (IR) and obesity are important risk factors for non-alcoholic fatty liver disease (NAFLD). G protein-coupled receptor kinase 2 (GRK2) is involved in the development of IR and obesity in vivo. However, its possible contribution to NAFLD and/or non-alcoholic steatohepatitis (NASH) independently of its role on IR or fat mass accretion has not been explored. Here, we used wild-type (WT) or GRK2 hemizygous (GRK2±) mice fed a high-fat diet (HFD) or a methionine and choline-deficient diet (MCD) as a model of NASH independent of adiposity and IR. GRK2± mice were protected from HFD-induced NAFLD. Moreover, MCD feeding caused an increased in triglyceride content and liver-to-body weight ratio in WT mice, features that were attenuated in GRK2± mice. According to their NAFLD activity score, MCD-fed GRK2± mice were diagnosed with simple steatosis and not overt NASH. They also showed reduced expression of lipogenic and lipid-uptake markers and less signs of inflammation in the liver. GRK2± mice preserved hepatic protective mechanisms as enhanced autophagy and mitochondrial fusion and biogenesis, together with reduced endoplasmic reticulum stress. GRK2 protein was increased in MCD-fed WT but not in GRK2± mice, and enhanced GRK2 expression potentiated palmitic acid-triggered lipid accumulation in human hepatocytes directly relating GRK2 levels to steatosis. GRK2 protein and mRNA levels were increased in human liver biopsies from simple steatosis or NASH patients in two different human cohorts. Our results describe a functional relationship between GRK2 levels and hepatic lipid accumulation and implicate GRK2 in the establishment and/or development of NASH. 相似文献
82.
Enrique Rozengurt James Sinnett-Smith Johan Van Lint Angela M. Valverde 《Mutation research》1995,333(1-2):153-160
A novel serine/threonine protein kinase regulated by phorbol esters and diacylglycerol (named PKD) has been identified. PKD contains a cysteine-rich repeat sequence homologous to that seen in the regulatory domain of protein kinase C (PKC). A bacterially expressed NH2-terminal domain of PKD exhibited high affinity phorbol ester binding activity (Kd = 35 nM). Expression of PKD cDNA in COS cells conferred increased phorbol ester binding to intact cells. The catalytic domain of PKD contains all characteristic sequence motifs of serine protein kinases but shows only a low degree of sequence similarity to PKCs. The bacterially expressed catalytic domain of PKD efficiently phosphorylated the exogenous peptide substrate syntide-2 in serine but did not catalyse significant phosphorylation of a variety of other substrates utilised by PKCs and other major second messenger regulated kinases. PKD expressed in COS cells showed syntide-2 kinase activity that was stimulated by phorbol esters in the presence of phospholipids. We propose that PKD may be a novel component in the transduction of diacylglycerol and phorbol ester signals. 相似文献
83.
P.E. Peterson J.J. Short R. Tarara C. Valverde E. Rothgarn A.G. Hendrickx 《Journal of medical primatology》1997,26(5):267-275
Abstract: This paper summarizes the spontaneous incidence of congenital defects in the rhesus and cynomolgus macaque colonies (Macaca mulatta and M. fascicularis) at the California Regional Primate Research Center. The computerized database used in this analysis included fetuses, term infants, juveniles, and adults that underwent a necropsy procedure over a 14-year period (1983–1996). The calculated malformation rates were 0.9% (40/4,390) and 0.3% (3/965) for the rhesus and cynomolgus monkey, respectively. Most of the observed malformations in both species affected the musculoskeletal and the cardiovascular systems, while a smaller number of defects were observed in the gastrointestinal, urogenital, endocrine, and central nervous systems. Inbreeding did not contribute to the spontaneous malformation incidence and there was no predilection for sex (male vs. female) or housing (indoors vs. outdoors) among the malformed cases. This spontaneous malformation database in our macaque colony aids in the interpretation of defects that occur in an experimental study as well as in the ongoing assessment of a healthy nonhuman primate breeding colony. 相似文献
84.
The Resplendent Quetzal (Pharomachrus mocinno) is an altitudinal migrant that nests in high elevation cloud forests and migrates toward lower areas during the summer rainy season. It has been suggested that its migratory movements are related to the abundance of ripe Lauraceae fruits. We studied the quetzal diet during two consecutive years, as well as changes in fruit abundance of the plant species on which the bird feeds at El Triunfo Biosphere Reserve, southeastern Mexico. The quetzal was observed feeding on 32 plant species; of these, 24 are new records in its diet. We chose 20 of these 32 species and studied their fruit phenology for two years in order to describe the relationship between fruit and quetzal abundance. Our results showed that quetzal abundance in the breeding area was correlated with the total number of fruiting species, whereas the correlation between quetzal abundance and the number of fruiting Lauraceae species was only marginal. Additionally, a correlation test showed that quetzal abundance was marginally correlated with total fruit availability (total no. of fruits per month); however, the correlation between quetzal abundance and the number of fruits in the Lauraceae was not significant. Our results suggest that the dynamics of food resources may be playing a major role in the quetzal's migratory behavior. Knowing the bird's diet may aid in characterizing the type of habitat adequate for its conservation. Our observations in this respect suggest that conservation efforts to preserve this bird species should concentrate on the protection of its habitat, including both breeding and nonbreeding (migration) locations. 相似文献
85.
86.
Four new diterpenes have been isolated from Sideritis serata: lagascol (4, ent-8,5-friedopimar-5-ene-15S,16-diol), tobarrol (8, ent-15-beyerene-12α,17-diol), benuol (12, ent-15-beyerene-7α,17-diol) and serradiol (18, ent-16R-atis-13-ene-16,17-diol). The previously known diterpenes lagascatriol (1, ent-8,5-friedopimar-5-ene-11β,15S,16-triol), jativatriol (2, ent-15-beyerene-1β,12α,17-triol), conchitriol (3, ent-15-beyerene-7α,12α,17-triol) and sideritol (17, ent-16R-atis-13-ene-1β,16,17-triol) have also been obtained from the same source. 相似文献
87.
88.
Above a threshold value in excess of 5.6 mM, D-glucose increases the amount of cyclic AMP measured by radioimmunoassay in pancreatic rat islets and their surrounding incubation medium. As judged from the cyclic AMP content of islets exposed to isobutylmethylxanthine (1.0 mM), the glucose-induced increment in the rate of cyclic AMP generation represents a rapid and sustained phenomenon. The stimulant action of glucose on cyclic AMP accumulation is mimicked by L-leucine, and L-glutamine, these amino acids acting synergistically of one another. Trifluoperazine slightly decreases but fails to abolish the effect of glucose. In the absence of extracellular Ca2+, however, the cyclic AMP response to D-glucose, L-leucine and/or L-glutamine is severely impaired. These findings are compatible with the view that an increase in the generation rate of cyclic AMP participates in the process of nutrient-stimulated insulin release. This increase could be secondary to the nutrient-induced accumulation of Ca2+ in the islet cells leading to activation of adenylate cyclase by calmodulin. 相似文献
89.
Three new diterpenoids have been detected in Salvia oxyodon and identified as 3β-hydroxy-dehydroabietic acid, 3β-acetoxy-abieta-8(14)-en-18-oic acid 9α,13α-endoperoxide and 3β-hydroxy-abieta-8(14)-en-18-oic acid 9α,13α-endoperoxide. Salvia lavandulifolia yielded two known compounds ursolic acid and galdosol. 相似文献
90.
Maria C. García-Alvarez Benjamín Rodríguez Serafin Valverde Braulio M. Fragat Antonio G. Gonzaléz 《Phytochemistry》1981,20(1):167-169
The 13C NMR signals of the parent hydrocarbon ent-rosa-5,15-diene (ent-(8,5-friedo-pimara-5,15-diene)and some of their oxygenated derivatives have been assigned. 相似文献