全文获取类型
收费全文 | 9210篇 |
免费 | 673篇 |
国内免费 | 2篇 |
专业分类
9885篇 |
出版年
2024年 | 4篇 |
2023年 | 51篇 |
2022年 | 126篇 |
2021年 | 219篇 |
2020年 | 132篇 |
2019年 | 172篇 |
2018年 | 226篇 |
2017年 | 188篇 |
2016年 | 312篇 |
2015年 | 500篇 |
2014年 | 581篇 |
2013年 | 682篇 |
2012年 | 819篇 |
2011年 | 841篇 |
2010年 | 550篇 |
2009年 | 425篇 |
2008年 | 555篇 |
2007年 | 559篇 |
2006年 | 484篇 |
2005年 | 499篇 |
2004年 | 421篇 |
2003年 | 399篇 |
2002年 | 346篇 |
2001年 | 80篇 |
2000年 | 56篇 |
1999年 | 81篇 |
1998年 | 90篇 |
1997年 | 64篇 |
1996年 | 54篇 |
1995年 | 56篇 |
1994年 | 45篇 |
1993年 | 41篇 |
1992年 | 24篇 |
1991年 | 26篇 |
1990年 | 27篇 |
1989年 | 17篇 |
1988年 | 13篇 |
1987年 | 11篇 |
1986年 | 13篇 |
1985年 | 9篇 |
1984年 | 11篇 |
1983年 | 13篇 |
1982年 | 15篇 |
1981年 | 11篇 |
1980年 | 5篇 |
1979年 | 5篇 |
1978年 | 7篇 |
1977年 | 5篇 |
1976年 | 5篇 |
1975年 | 3篇 |
排序方式: 共有9885条查询结果,搜索用时 15 毫秒
51.
Zhang HC Ye H Conway BR Derian CK Addo MF Kuo GH Hecker LR Croll DR Li J Westover L Xu JZ Look R Demarest KT Andrade-Gordon P Damiano BP Maryanoff BE 《Bioorganic & medicinal chemistry letters》2004,14(12):3245-3250
A novel series of acyclic 3-(7-azaindolyl)-4-(aryl/heteroaryl)maleimides was synthesized and evaluated for activity against GSK-3beta and selectivity versus PKC-betaII, as well as a broad panel of protein kinases. Compounds 14 and 17c potently inhibited GSK-3beta (IC(50)=7 and 26 nM, respectively) and exhibited excellent selectivity over PKC-betaII (325 and >385-fold, respectively). Compound 17c was also highly selective against 68 other protein kinases. In a cell-based functional assay, both 14 and 17c effectively increased glycogen synthase activity by inhibiting GSK-3beta. 相似文献
52.
Recent years have seen several advances in our understanding of the functions of adipose tissue regarding not only the energy storage, but also the regulation of complex metabolic and endocrine functions. In this context, leptin and adiponectin, the two most abundant adipocyte products, represent one of the best example of adipocytokines involved in the control of energy expenditure, lipid and carbohydrate metabolism as well as in the regulation of immune responses. Leptin and adiponectin secretion is counter-regulated in vivo, in relation to degree of adiposity, since plasma leptin concentrations are significantly elevated in obese subjects in proportion to body mass index while adiponectin secretion decreases in relation to the amount of adipose tissue. In this review we focus on the main biological activities of leptin and adiponectin on the lipid and carbohydrate metabolism and on their contribute in regulation of innate and adaptive immune responses. 相似文献
53.
Maria Cristiane Rabelo Claudia P.M.L. Fontes Sueli Rodrigues 《Bioresource technology》2009,100(23):5574-5580
The use of agriculture substrates in industrial biotechnological processes has been increasing because of their low cost. In this work, the use of clarified cashew apple juice was investigated as substrate for enzyme synthesis of prebiotic oligosaccharide. The results showed that cashew apple juice is a good source of reducing sugars and can be used as substrate for the production of dextransucrase by Leuconostoc citreum B-742 for the synthesis of oligosaccharides using the crude enzyme. Optimal oligosaccharide yield (approximately 80%) was obtained for sucrose concentrations lower than 60 g/L and reducing sugar concentrations higher than 100 g/L. 相似文献
54.
55.
The mammalian genome is organized as a mosaic of isochores, stretches of DNA with a distinct sequence composition. Isochores form the basis of the chromosomal banding pattern, which is tightly correlated with a number of structural and functional features. We have recently demonstrated that the transition from a GC-poor isochore to a GC-rich one in the NF1 gene region occurs within 5 kb and demarcates genomic regions with high and low recombination frequency. We now report that the same transition zone separates early replicating from late replicating chromatin on the molecular level. At the isochore transition the replication fork is stalled in mid-S phase and can be visualized by fiber-FISH techniques as a Y-shaped structure. The switch in GC content and in replication timing is conserved between human and mouse, emphasizing the importance of the transition zones as landmarks of chromosome organization and function. 相似文献
56.
57.
58.
Identification of the minimal protein domain required for priming activity of Munc13-1 总被引:1,自引:0,他引:1
Stevens DR Wu ZX Matti U Junge HJ Schirra C Becherer U Wojcik SM Brose N Rettig J 《Current biology : CB》2005,15(24):2243-2248
Most nerve cells communicate with each other through synaptic transmission at chemical synapses. The regulated exocytosis of neurotransmitters, hormones, and peptides occurs at specialized membrane areas through Ca2+-triggered fusion of secretory vesicles with the plasma membrane . Prior to fusion, vesicles are docked at the plasma membrane and must then be rendered fusion-competent through a process called priming. The molecular mechanism underlying this priming process is most likely the formation of the SNARE complex consisting of Syntaxin 1, SNAP-25, and Synaptobrevin 2. Members of the Munc13 protein family consisting of Munc13-1, -2, -3, and -4 were found to be absolutely required for this priming process . In the present study, we identified the minimal Munc13-1 domain that is responsible for its priming activity. Using Munc13-1 deletion constructs in an electrophysiological gain-of-function assay of chromaffin-granule secretion, we show that priming activity is mediated by the C-terminal residues 1100-1735 of Munc13-1, which contains both Munc13-homology domains and the C-terminal C2 domain. Priming by Munc13-1 appears to require its interaction with Syntaxin 1 because point mutants that do not bind Syntaxin 1 do not prime chromaffin granules. 相似文献
59.
Palynomorph assemblages have been recovered from deposits believed to straddle the Ordovician/Silurian boundary, from the upper member of the Salar del Rincón Formation, in the Puna region of north-west Argentina. The palynomorph assemblages are dominated by terrestrial cryptospores, but also contain marine elements (acritarchs, prasinophycean algae and chitinozoans). The cryptospore assemblages are similar in composition to those described from coeval deposits worldwide, suggesting that the producers were cosmopolitan and tolerated a wide range of climatic conditions. They are correlated with the Imperfectotriletes spp. Interval Biozone (sub-biozone α) of the Imperfectotriletes spp.- Laevolancis divellomedia Assemblage Biozone, indicating a Hirnantian (latest Ordovician) age. Acritarchs include late Ordovician species such as Eupoikilosusa striata and Villosacapsula cf. setosapellicula , that coexist with the Llandovery species Dactylofusa estillis. Based on lithological and palynological evidence, an early Llandovery, or a late Hirnantian (post-glacial) age is proposed for the basal part of the upper member of the Salar del Rincón Formation. 相似文献
60.
Rivara M Vacondio F Silva C Zuliani V Fantini M Bordi F Plazzi PV Bertoni S Ballabeni V Flammini L Barocelli E Mor M 《化学与生物多样性》2008,5(1):140-152
A series of carbamate derivatives of the H(3) antagonist ROS203 (1) were prepared, and their lipophilicity and steric hindrance were modulated by introducing linear or branched alkyl chains of various lengths. In vitro stability studies were conducted to evaluate how structural modulations affect the intrinsic reactivity of the carbamoyl moiety and its recognition by metabolic enzymes. Linear alkyl carbamates were the most susceptible to enzymatic hydrolysis, with bioconversion rates being higher in rat liver and plasma. Chain ramification significantly enhanced the enzymatic stability of the set, with two derivatives (1g and 1h) being more stable by a factor of 8-40 than the ethyl carbamate 1a. Incubation with bovine serum albumin (BSA) showed a protective role of proteins on chemical and porcine-liver esterase (PLE)-catalyzed hydrolysis. Ex vivo binding data after i.v. administration of 1h revealed prolonged displacement of the labeled ligand [(3)H]-(R)-alpha-methylhistamine ([(3)H]RAMHA) from rat-brain cortical membranes, when compared to 1. However, the high rates of bioconversion in liver, as well as the chemical instability of 1h, suggest that further work is needed to optimize the enzymatic and chemical stability of these compounds. 相似文献