全文获取类型
收费全文 | 772篇 |
免费 | 66篇 |
专业分类
838篇 |
出版年
2024年 | 1篇 |
2023年 | 3篇 |
2022年 | 9篇 |
2021年 | 19篇 |
2020年 | 10篇 |
2019年 | 11篇 |
2018年 | 20篇 |
2017年 | 10篇 |
2016年 | 23篇 |
2015年 | 38篇 |
2014年 | 36篇 |
2013年 | 52篇 |
2012年 | 55篇 |
2011年 | 65篇 |
2010年 | 39篇 |
2009年 | 36篇 |
2008年 | 53篇 |
2007年 | 59篇 |
2006年 | 56篇 |
2005年 | 55篇 |
2004年 | 57篇 |
2003年 | 38篇 |
2002年 | 39篇 |
2001年 | 5篇 |
2000年 | 7篇 |
1999年 | 6篇 |
1998年 | 2篇 |
1997年 | 3篇 |
1996年 | 6篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1982年 | 1篇 |
1977年 | 1篇 |
1975年 | 1篇 |
1967年 | 1篇 |
1958年 | 1篇 |
1956年 | 1篇 |
排序方式: 共有838条查询结果,搜索用时 15 毫秒
41.
Lipophylic compounds from Euphorbia peplis L.--a halophytic plant from the Bulgarian Black Sea coast
Ivanova A Khozin-Goldberg I Kamenarska Z Nechev J Cohen Z Popov S Stefanov K 《Zeitschrift für Naturforschung. C, Journal of biosciences》2003,58(11-12):783-788
The chemical composition of the lipophylic fraction from the halophytic plant Euphorbia peplis L. was investigated. Compared to other terrestrial higher plants an increase of triacylglycerols and especially of glycolipids was observed. The main phospholipid was phosphatidyl choline, followed by almost equal concentrations of phosphatidyl ethanolamine and phosphatidyl glycerol. A relatively high concentration of phosphatidic acids (6.5% of the total phospholipids) was found. The main sterol appeared to be sitosterol and significant amounts of tetracyclic triterpene alcohols were found. The composition of the volatile compounds is relatively simple and only one chlorinated compound, identified as 2,2-diethoxy-1-chloroethane, was found. There was a strong toxicity of the total lipophylic extract towards Artemia salina. 相似文献
42.
Schwarzenbacher R Jaroszewski L von Delft F Abdubek P Ambing E Biorac T Brinen LS Canaves JM Cambell J Chiu HJ Dai X Deacon AM DiDonato M Elsliger MA Eshagi S Floyd R Godzik A Grittini C Grzechnik SK Hampton E Karlak C Klock HE Koesema E Kovarik JS Kreusch A Kuhn P Lesley SA Levin I McMullan D McPhillips TM Miller MD Morse A Moy K Ouyang J Page R Quijano K Robb A Spraggon G Stevens RC van den Bedem H Velasquez J Vincent J Wang X West B Wolf G Xu Q Hodgson KO Wooley J Wilson IA 《Proteins》2004,55(3):759-763
43.
Goncharov Alexey I. Levina Inna S. Shliapina Viktoriia L. Morozov Ivan A. Rubtsov Petr M. Zavarzin Igor V. Smirnova Olga V. Shchelkunova Tatiana A. 《Biochemistry. Biokhimii?a》2021,86(11):1446-1460
Biochemistry (Moscow) - Progesterone and its synthetic analogues act on cells through different types of receptors, affecting proliferation and apoptosis. These compounds exert their effect through... 相似文献
44.
45.
Omera B. Matoo Anna V. Ivanina Claus Ullstad Elia Beniash Inna M. Sokolova 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2013,164(4):545-553
Marine bivalves such as the hard shell clams Mercenaria mercenaria and eastern oysters Crassostrea virginica are affected by multiple stressors, including fluctuations in temperature and CO2 levels in estuaries, and these stresses are expected to be exacerbated by ongoing global climate change. Hypercapnia (elevated CO2 levels) and temperature stress can affect survival, growth and development of marine bivalves, but the cellular mechanisms of these effects are not yet fully understood. In this study, we investigated whether oxidative stress is implicated in cellular responses to elevated temperature and CO2 levels in marine bivalves. We measured the whole-organism standard metabolic rate (SMR), total antioxidant capacity (TAOC), and levels of oxidative stress biomarkers in the muscle tissues of clams and oysters exposed to different temperatures (22 and 27 °C) and CO2 levels (the present day conditions of ~ 400 ppm CO2 and 800 ppm CO2 predicted by a consensus business-as-usual IPCC emission scenario for the year 2100). SMR was significantly higher and the antioxidant capacity was lower in oysters than in clams. Aerobic metabolism was largely temperature-independent in these two species in the studied temperature range (22–27 °C). However, the combined exposure to elevated temperature and hypercapnia led to elevated SMR in clams indicating elevated costs of basal maintenance. No persistent oxidative stress signal (measured by the levels of protein carbonyls, and protein conjugates with malondialdehyde and 4-hydroxynonenal) was observed during the long-term exposure to moderate warming (+ 5 °C) and hypercapnia (~ 800 ppm CO2). This indicates that long-term exposure to moderately elevated CO2 and temperature minimally affects the cellular redox status in these bivalve species and that the earlier observed negative physiological effects of elevated CO2 and temperature must be explained by other cellular mechanisms. 相似文献
46.
Considerable progress has been made recently toward understanding the processes of mitochondrial DNA (mtDNA) damage and repair. However, a paucity of information still exists regarding the physiological effects of persistent mtDNA damage. This is due, in part, to experimental difficulties associated with targeting mtDNA for damage, while sparing nuclear DNA. Here, we characterize two systems designed for targeted mtDNA damage based on the inducible (Tet-ON) mitochondrial expression of the bacterial enzyme, exonuclease III, and the human enzyme, uracil-N-glyosylase containing the Y147A mutation. In both systems, damage was accompanied by degradation of mtDNA, which was detectable by 6 h after induction of mutant uracil-N-glycosylase and by 12 h after induction of exoIII. Unexpectedly, increases in the steady-state levels of single-strand lesions, which led to degradation, were small in absolute terms indicating that both abasic sites and single-strand gaps may be poorly tolerated in mtDNA. mtDNA degradation was accompanied by the loss of expression of mtDNA-encoded COX2. After withdrawal of the inducer, recovery from mtDNA depletion occurred faster in the system expressing exonuclease III, but in both systems reduced mtDNA levels persisted longer than 144 h after doxycycline withdrawal. mtDNA degradation was followed by reduction and loss of respiration, decreased membrane potential, reduced cell viability, reduced intrinsic reactive oxygen species production, slowed proliferation, and changes in mitochondrial morphology (fragmentation of the mitochondrial network, rounding and “foaming” of the mitochondria). The mutagenic effects of abasic sites in mtDNA were low, which indicates that damaged mtDNA molecules may be degraded if not rapidly repaired. This study establishes, for the first time, that mtDNA degradation can be a direct and immediate consequence of persistent mtDNA damage and that increased ROS production is not an invariant consequence of mtDNA damage. 相似文献
47.
Altered nuclear distribution of recombination protein RAD51 in maize mutants suggests the involvement of RAD51 in meiotic homology recognition 总被引:12,自引:0,他引:12 下载免费PDF全文
The recombination protein RAD51 is a component of the meiotic recombination pathway and has been proposed to play a role in the homology search, a process by which homologous chromosomes find each other before they pair in the prophase of meiosis. To study the relationship between recombination and chromosome pairing, we examined the distribution of RAD51 foci on meiotic chromosomes in maize mutants with defects in chromosome pairing. The patterns of RAD51 distribution showed dramatic variation among the meiotic mutants. The mutants generally exhibited significant decreases in the number of RAD51 foci at zygotene, corresponding to the degree of their pairing defects. These results provide evidence for a key role of RAD51 structures in the homology search. 相似文献
48.
Foltyn VN Bendikov I De Miranda J Panizzutti R Dumin E Shleper M Li P Toney MD Kartvelishvily E Wolosker H 《The Journal of biological chemistry》2005,280(3):1754-1763
Mammalian brain contains high levels of d-serine, an endogenous co-agonist of N-methyl D-aspartate type of glutamate receptors. D-Serine is synthesized by serine racemase, a brain enriched enzyme converting L- to D-serine. Degradation of D-serine is achieved by D-amino acid oxidase, but this enzyme is not present in forebrain areas that are highly enriched in D-serine. We now report that serine racemase catalyzes the degradation of cellular D-serine itself, through the alpha,beta-elimination of water. The enzyme also catalyzes water alpha,beta-elimination with L-serine and L-threonine. alpha,beta-Elimination with these substrates is observed both in vitro and in vivo. To investigate further the role of alpha,beta-elimination in regulating cellular D-serine, we generated a serine racemase mutant displaying selective impairment of alpha,beta-elimination activity (Q155D). Levels of D-serine synthesized by the Q155D mutant are several-fold higher than the wild-type both in vitro and in vivo. This suggests that the alpha,beta-elimination reaction limits the achievable D-serine concentration in vivo. Additional mutants in vicinal residues (H152S, P153S, and N154F) similarly altered the partition between the alpha,beta-elimination and racemization reactions. alpha,beta-Elimination also competes with the reverse serine racemase reaction in vivo. Although the formation of L- from D-serine is readily detected in Q155D mutant-expressing cells incubated with physiological D-serine concentrations, reversal with wild-type serine racemase-expressing cells required much higher D-serine concentration. We propose that alpha,beta-elimination provides a novel mechanism for regulating intracellular D-serine levels, especially in brain areas that do not possess D-amino acid oxidase activity. Extracellular D-serine is more stable toward alpha,beta-elimination, likely due to physical separation from serine racemase and its elimination activity. 相似文献
49.
Reigle KL Di Lullo G Turner KR Last JA Chervoneva I Birk DE Funderburgh JL Elrod E Germann MW Surber C Sanderson RD San Antonio JD 《Journal of cellular biochemistry》2008,104(5):1684-1698
Non-enzymatic glycation of type I collagen occurs in aging and diabetes, and may affect collagen solubility, charge, polymerization, and intermolecular interactions. Proteoglycans(1) (PGs) bind type I collagen and are proposed to regulate fibril assembly, function, and cell-collagen interactions. Moreover, on the collagen fibril a keratan sulfate (KS) PG binding region overlaps with preferred collagen glycation sites. Thus, we examined the effect of collagen modified by simple glycation on PG-collagen interactions. By affinity coelectrophoresis (ACE), we found reduced affinities of heparin and KSPGs for glycated but not normal collagen, whereas the dermatan sulfate (DS)PGs decorin and biglycan bound similarly to both, and that the affinity of heparin for normal collagen decreased with increasing pH. Circular dichroism (CD) spectroscopy revealed normal and glycated collagens to assume triple helical conformations, but heparin addition caused precipitation and decreased triple helical content-effects that were more marked with glycated collagen. A spectrophotometric assay revealed slower polymerization of glycated collagen. However, ultrastructural analyses indicated that fibrils assembled from normal and glycated collagen exhibited normal periodicity, and had similar structures and comparable diameter distributions. B-cells expressing the cell surface heparan sulfate PG syndecan-1 adhered well to normal but not glycated collagen, and endothelial cell migration was delayed on glycated collagen. We speculate that glycation diminishes the electrostatic interactions between type I collagen and PGs, and may interfere with core protein-collagen associations for KSPGs but not DSPGs. Therefore in vivo, collagen glycation may weaken PG-collagen interactions, thereby disrupting matrix integrity and cell-collagen interactions, adhesion, and migration. 相似文献
50.
Lipids revert inert Abeta amyloid fibrils to neurotoxic protofibrils that affect learning in mice 总被引:1,自引:0,他引:1 下载免费PDF全文
Martins IC Kuperstein I Wilkinson H Maes E Vanbrabant M Jonckheere W Van Gelder P Hartmann D D'Hooge R De Strooper B Schymkowitz J Rousseau F 《The EMBO journal》2008,27(1):224-233
Although soluble oligomeric and protofibrillar assemblies of Abeta-amyloid peptide cause synaptotoxicity and potentially contribute to Alzheimer's disease (AD), the role of mature Abeta-fibrils in the amyloid plaques remains controversial. A widely held view in the field suggests that the fibrillization reaction proceeds 'forward' in a near-irreversible manner from the monomeric Abeta peptide through toxic protofibrillar intermediates, which subsequently mature into biologically inert amyloid fibrils that are found in plaques. Here, we show that natural lipids destabilize and rapidly resolubilize mature Abeta amyloid fibers. Interestingly, the equilibrium is not reversed toward monomeric Abeta but rather toward soluble amyloid protofibrils. We characterized these 'backward' Abeta protofibrils generated from mature Abeta fibers and compared them with previously identified 'forward' Abeta protofibrils obtained from the aggregation of fresh Abeta monomers. We find that backward protofibrils are biochemically and biophysically very similar to forward protofibrils: they consist of a wide range of molecular masses, are toxic to primary neurons and cause memory impairment and tau phosphorylation in mouse. In addition, they diffuse rapidly through the brain into areas relevant to AD. Our findings imply that amyloid plaques are potentially major sources of soluble toxic Abeta-aggregates that could readily be activated by exposure to biological lipids. 相似文献