全文获取类型
收费全文 | 1583篇 |
免费 | 113篇 |
国内免费 | 32篇 |
专业分类
1728篇 |
出版年
2023年 | 22篇 |
2022年 | 33篇 |
2021年 | 43篇 |
2020年 | 52篇 |
2019年 | 70篇 |
2018年 | 54篇 |
2017年 | 57篇 |
2016年 | 72篇 |
2015年 | 54篇 |
2014年 | 60篇 |
2013年 | 122篇 |
2012年 | 60篇 |
2011年 | 50篇 |
2010年 | 38篇 |
2009年 | 70篇 |
2008年 | 66篇 |
2007年 | 70篇 |
2006年 | 65篇 |
2005年 | 60篇 |
2004年 | 57篇 |
2003年 | 50篇 |
2002年 | 43篇 |
2001年 | 29篇 |
2000年 | 22篇 |
1999年 | 26篇 |
1998年 | 36篇 |
1997年 | 40篇 |
1996年 | 24篇 |
1995年 | 19篇 |
1994年 | 33篇 |
1993年 | 23篇 |
1992年 | 29篇 |
1991年 | 18篇 |
1990年 | 17篇 |
1989年 | 13篇 |
1988年 | 19篇 |
1987年 | 13篇 |
1986年 | 20篇 |
1985年 | 10篇 |
1984年 | 15篇 |
1983年 | 4篇 |
1982年 | 6篇 |
1981年 | 4篇 |
1980年 | 10篇 |
1979年 | 5篇 |
1978年 | 6篇 |
1976年 | 2篇 |
1973年 | 3篇 |
1972年 | 4篇 |
1970年 | 5篇 |
排序方式: 共有1728条查询结果,搜索用时 0 毫秒
81.
82.
83.
84.
Bee dietary preferences,or the floral resources that they consistently collect,likely impact where a species can persist.For this reason it is likely that bee dietary preferences are dependent upon the composition of the plant community.In this study,we evaluated floral visits and pollen loads of the mining bee,Andrena angustitarsata Viereck,across a 630 km north-south range to understand dietary preferences along a floral resource gradient.Previous research,in a more geographically limited area,suggested this species was an eclectic oligolege on predominantly Apiaceae and in part Rosaceae.In the present study we found the species predominately visited and collected pollen from Apiaceae and Rosaceae,but visited 12 flower families and collected pollen from 32,distinguishing them as generalist foragers.The frequency of Apiaceae pollen on the bees and the species-level specialization index(a measure of visit specialization)were higher in regions with higher Apiaceae abundance.In addition Apiaceae and Rosaceae were the only plant families significantly preferred for pollen collection,regardless of floral abundance.We conclude that across our study region A.angustitarsata has a generalist dietary breadth,but also has dietary preference for Apiaceae and Rosaceae.Our study indicates that while bees may overall make generalist foraging decisions they may still prefer and likely benefit from selecting fewer flower taxa. 相似文献
85.
Michael R. Heaven Anthony W. Herren Daniel L. Flint Natasha L. Pacheco Jiangtao Li Alice Tang Fatima Khan James E. Goldman Brett S. Phinney Michelle L. Olsen 《Molecular & cellular proteomics : MCP》2022,21(1):100180
Alexander disease (AxD) is a rare and fatal neurodegenerative disorder caused by mutations in the gene encoding glial fibrillary acidic protein (GFAP). In this report, a mouse model of AxD (GFAPTg;Gfap+/R236H) was analyzed that contains a heterozygous R236H point mutation in murine Gfap as well as a transgene with a GFAP promoter to overexpress human GFAP. Using label-free quantitative proteomic comparisons of brain tissue from GFAPTg;Gfap+/R236H versus wild-type mice confirmed upregulation of the glutathione metabolism pathway and indicated proteins were elevated in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which had not been reported previously in AxD. Relative protein-level differences were confirmed by a targeted proteomics assay, including proteins related to astrocytes and oligodendrocytes. Of particular interest was the decreased level of the oligodendrocyte protein, 2-hydroxyacylsphingosine 1-beta-galactosyltransferase (Ugt8), since Ugt8-deficient mice exhibit a phenotype similar to GFAPTg;Gfap+/R236H mice (e.g., tremors, ataxia, hind-limb paralysis). In addition, decreased levels of myelin-associated proteins were found in the GFAPTg;Gfap+/R236H mice, consistent with the role of Ugt8 in myelin synthesis. Fabp7 upregulation in GFAPTg;Gfap+/R236H mice was also selected for further investigation due to its uncharacterized association to AxD, critical function in astrocyte proliferation, and functional ability to inhibit the anti-inflammatory PPAR signaling pathway in models of amyotrophic lateral sclerosis (ALS). Within Gfap+ astrocytes, Fabp7 was markedly increased in the hippocampus, a brain region subjected to extensive pathology and chronic reactive gliosis in GFAPTg;Gfap+/R236H mice. Last, to determine whether the findings in GFAPTg;Gfap+/R236H mice are present in the human condition, AxD patient and control samples were analyzed by Western blot, which indicated that Type I AxD patients have a significant fourfold upregulation of FABP7. However, immunohistochemistry analysis showed that UGT8 accumulates in AxD patient subpial brain regions where abundant amounts of Rosenthal fibers are located, which was not observed in the GFAPTg;Gfap+/R236H mice. 相似文献
86.
真核生物的DNA以染色质形式通过逐级折叠压缩形成高级结构存在于细胞核中。染色质高级结构直接参与了真核基因的转录调控和其它与DNA相关的生物学事件,因此研究染色质高级结构对了解表观遗传学分子机制有着至关重要的作用。近些年,研究者们针对30 nm染色质高级结构提出了两个模型:螺线管模型和Zig-Zag模型。2014年,我们利用体外染色质组装体系重建了30 nm染色质纤维,运用高精度冷冻电镜技术得到了分辨率为11?的30 nm染色质纤维的精细结构,提出了30 nm染色质高级结构的左手双螺旋Zig-Zag模型。本文综述了30 nm染色质纤维结构研究方面的相关进展,并对30 nm染色质高级结构的表观遗传调控机理以及单分子成像和操纵技术在研究30 nm染色质高级结构中潜在的应用作出讨论和展望。 相似文献
87.
Marta Murgia Nagarjuna Nagaraj Atul S Deshmukh Marlis Zeiler Pasqua Cancellara Irene Moretti Carlo Reggiani Stefano Schiaffino Matthias Mann 《EMBO reports》2015,16(3):387-395
Mammalian skeletal muscles are composed of multinucleated cells termed slow or fast fibers according to their contractile and metabolic properties. Here, we developed a high‐sensitivity workflow to characterize the proteome of single fibers. Analysis of segments of the same fiber by traditional and unbiased proteomics methods yielded the same subtype assignment. We discovered novel subtype‐specific features, most prominently mitochondrial specialization of fiber types in substrate utilization. The fiber type‐resolved proteomes can be applied to a variety of physiological and pathological conditions and illustrate the utility of single cell type analysis for dissecting proteomic heterogeneity. 相似文献
88.
Sun X Komatsu T Lim J Laslo M Yolitz J Wang C Poirier L Alberico T Zou S 《Aging cell》2012,11(5):783-793
Reactive oxygen species (ROS) modulate aging and aging-related diseases. Dietary composition is critical in modulating lifespan. However, how ROS modulate dietary effects on lifespan remains poorly understood. Superoxide dismutase 1 (SOD1) is a major cytosolic enzyme responsible for scavenging superoxides. Here we investigated the role of SOD1 in lifespan modulation by diet in Drosophila. We found that a high sugar-low protein (HS-LP) diet or low-calorie diet with low-sugar content, representing protein restriction, increased lifespan but not resistance to acute oxidative stress in wild-type flies, relative to a standard base diet. A low sugar-high protein diet had an opposite effect. Our genetic analysis indicated that SOD1 overexpression or dfoxo deletion did not alter lifespan patterns of flies responding to diets. However, sod1 reduction blunted lifespan extension by the HS-LP diet but not the low-calorie diet. HS-LP and low-calorie diets both reduced target of rapamycin (TOR) signaling and only the HS-LP diet increased oxidative damage. sod1 knockdown did not affect phosphorylation of S6 kinase, suggesting that SOD1 acts in parallel with or downstream of TOR signaling. Surprisingly, rapamycin decreased lifespan in sod1 mutant but not wild-type males fed the standard, HS-LP, and low-calorie diets, whereas antioxidant N-acetylcysteine only increased lifespan in sod1 mutant males fed the HS-LP diet, when compared to diet-matched controls. Our findings suggest that SOD1 is required for lifespan extension by protein restriction only when dietary sugar is high and support the context-dependent role of ROS in aging and caution the use of rapamycin and antioxidants in aging interventions. 相似文献
89.
《Bioscience, biotechnology, and biochemistry》2013,77(8):1748-1754
The effects of different types of dietary fat on the activities of hepatic enzymes related to fatty acid synthesis {glucose-6-phosphate dehydrogenase (G6PDH) and acetyl-CoA carboxylase ACC)}, oxidation {acyl-CoA synthetase (AST), carnitine palmitoyl transferase (CPT), and peroxisomal β-oxidation (P βOX)}, and lipogenesis {phosphatidate phosphohydrolase (PAP), diacylglycerol acyltransferase (DGAT), and phosphocholine diacylglycerol transferase (PCDGT)}, and plasma and liver lipid levels were investigated in male Wistar rats. The animals were 6 weeks old and about 120 g of body weight, and were fed on test diets containing 20% of a mixture of tripalmitin, tristearin and corn oil (SFA), olive oil (OLI), sunflower oil (SUN), linseed oil (LIS), and sardine oil (SAR) for 2 weeks. The concentrations of plasma total cholesterol (T-CHOL), high-density lipoprotein-cholesterol (HDL-CHOL), triacylglycerol (TG) and phospholipid (PL) were generally higher in the rats fed on SEA and OLI than in those given SUN, LIS and SAR. The rats fed on OLI had a higher level of liver T-CHOL than those fed on the other fats. The liver TG content was nearly higher from the intake of SFA and OLI than from SUN, LIS and SAR, although the liver PL level was not affected by the type of dietary fat. The SFA and OLI groups had the highest activities of hepatic G6PDH and ACC, and the SAR group, the lowest activities. The activities of AST and CPT, and peroxisomal P βOX in the liver were higher in the rats fed on the LIS and SAR diets than in those given the other diets. The hepatic PAP activity was higher from the intake of OLI and SUN, and tended to be higher from SFA than from LIS and SAR. The activity of liver DGAT was higher from SFA and inclined to be higher from OLI, SUN, and LIS than from SAR, while the PCDGT activity in the liver was not effected by the type of dietary fat. The concentrations of plasma and liver TG were generally positively correlated with the activities of liver enzymes related to the synthesis of fatty acids and lipids, and negatively with those involved in fatty acid oxidation. Based on these results, it is suggested that the levels of plasma and liver TG were controlled by different types of dietary fat through changes in the hepatic enzyme activities related to fatty acid synthesis, lipogenesis, and fatty acid oxidation. 相似文献
90.
The protective effects of dietary Ca2+ supplementation against Cd accumulation in rainbow trout Oncorhynchus mykiss fed with Cd-contaminated food were evaluated in relation to chronic changes in intestinal absorption rates. The changes were measured ' in vitro '. The control diet contained c. 20 mg Ca2+ g−1 food and 0·25 μg Cd g−1 food; the experimental diets were supplemented with CaCO3 and Cd(NO3 )2 ·4H2 O to levels of 50 mg Ca2+ g−1 food and 300 μg Cd g−1 food, alone and in combination. The Ca2+ and Cd absorption rates were measured using radiotracers (45 Ca, 109 Cd) at total Ca2+ and Cd concentrations of 3·0 and 0·12 mmol l−1 , respectively in the intestinal saline. Chronically elevated dietary Cd caused a significant increase in Cd absorption rate by up to 10-fold at 30 days in the mid-intestine. The high Ca2+ diet prevented this up-regulation of Cd transport rate. Conversely, intestinal Ca2+ absorption was significantly increased by two- to five-fold by the Ca2+ -supplemented diet at 30 days in both the mid- and posterior intestine, and this effect was eliminated when Cd was simultaneously elevated in the diet. Ca2+ and Cd probably interact at common pathways and transport mechanisms in the intestine, though independent pathways may also exist. 相似文献