全文获取类型
收费全文 | 209篇 |
免费 | 0篇 |
专业分类
系统科学 | 1篇 |
理论与方法论 | 1篇 |
现状及发展 | 72篇 |
研究方法 | 54篇 |
综合类 | 65篇 |
自然研究 | 16篇 |
出版年
2020年 | 1篇 |
2019年 | 2篇 |
2018年 | 1篇 |
2017年 | 4篇 |
2016年 | 1篇 |
2015年 | 1篇 |
2014年 | 3篇 |
2013年 | 7篇 |
2012年 | 12篇 |
2011年 | 31篇 |
2010年 | 4篇 |
2009年 | 2篇 |
2008年 | 11篇 |
2007年 | 18篇 |
2006年 | 16篇 |
2005年 | 10篇 |
2004年 | 15篇 |
2003年 | 9篇 |
2002年 | 9篇 |
2000年 | 2篇 |
1989年 | 1篇 |
1986年 | 1篇 |
1982年 | 4篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1974年 | 1篇 |
1973年 | 4篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1970年 | 1篇 |
1969年 | 4篇 |
1968年 | 3篇 |
1967年 | 2篇 |
1965年 | 1篇 |
1964年 | 3篇 |
1963年 | 1篇 |
1962年 | 1篇 |
1961年 | 1篇 |
1958年 | 2篇 |
1957年 | 1篇 |
1956年 | 1篇 |
1955年 | 2篇 |
1954年 | 1篇 |
1948年 | 1篇 |
排序方式: 共有209条查询结果,搜索用时 15 毫秒
201.
The repair of DNA double-strand breaks (DSBs) is crucial for maintaining genome stability. Eukaryotic cells repair DSBs by both non-homologous end joining and homologous recombination. How chromatin structure is altered in response to DSBs and how such alterations influence DSB repair processes are important issues. In vertebrates, phosphorylation of the histone variant H2A.X occurs rapidly after DSB formation, spreads over megabase chromatin domains, and is required for stable accumulation of repair proteins at damage foci. In Saccharomyces cerevisiae, phosphorylation of the two principal H2A species is also signalled by DSB formation, which spreads approximately 40 kb in either direction from the DSB. Here we show that near a DSB phosphorylation of H2A is followed by loss of histones H2B and H3 and increased sensitivity of chromatin to digestion by micrococcal nuclease; however, phosphorylation of H2A and nucleosome loss occur independently. The DNA damage sensor MRX is required for histone loss, which also depends on INO80, a nucleosome remodelling complex. The repair protein Rad51 (ref. 6) shows delayed recruitment to DSBs in the absence of histone loss, suggesting that MRX-dependent nucleosome remodelling regulates the accessibility of factors directly involved in DNA repair by homologous recombination. Thus, MRX may regulate two pathways of chromatin changes: nucleosome displacement for efficient recruitment of homologous recombination proteins; and phosphorylation of H2A, which modulates checkpoint responses to DNA damage. 相似文献
202.
Mutant dynactin in motor neuron disease 总被引:24,自引:0,他引:24
Puls I Jonnakuty C LaMonte BH Holzbaur EL Tokito M Mann E Floeter MK Bidus K Drayna D Oh SJ Brown RH Ludlow CL Fischbeck KH 《Nature genetics》2003,33(4):455-456
Impaired axonal transport in motor neurons has been proposed as a mechanism for neuronal degeneration in motor neuron disease. Here we show linkage of a lower motor neuron disease to a region of 4 Mb at chromosome 2p13. Mutation analysis of a gene in this interval that encodes the largest subunit of the axonal transport protein dynactin showed a single base-pair change resulting in an amino-acid substitution that is predicted to distort the folding of dynactin's microtubule-binding domain. Binding assays show decreased binding of the mutant protein to microtubules. Our results show that dysfunction of dynactin-mediated transport can lead to human motor neuron disease. 相似文献
203.
Atlas R Campbell P Cozzarelli NR Curfman G Enquist L Fink G Flanagin A Fletcher J George E Hammes G Heyman D Inglesby T Kaplan S Kennedy D Krug J Levinson R Marcus E Metzger H Morse SS O'Brien A Onderdonk A Poste G Renault B Rich R Rosengard A Salzberg S Scanlan M Shenk T Tabor H Varmus H Wimmer E Yamamoto K;Journal Editors Authors Group 《Nature》2003,421(6925):771
204.
Mary S. Wheatley 《Cellular and molecular life sciences : CMLS》1956,12(9):339-340
Zusammenfassung Die Rekombinationsgeschwindigkeit von Phenylglyoxylationen und Hydroniumionen wird aufs neue in neutraler Lösung bestimmt, und es wird gezeigt, dass sie dem Wert, der von uns früher in alkalischer Lösung gefunden wurde, entspricht. Beide Werte stimmen auch mit den Literaturangaben überein.Die Rekombinationsgeschwindigkeiten einer Serie von substituierten Phenylglyoxylsäuren und die Rekombinationsgeschwindigkeit von Phenylglyoxylat- und Deuteroniumionen werden angegeben. 相似文献
205.
Résumé Dans un mémoire paru en 1941,Crabtree a décrit un cas unique de carcinogénèse chimique expérimentale dans lequel selon le degré de concentration ou selon l'ordre adopté pour le badigeonnage, le chloroacétone accélère ou inhibe l'apparition des tumeurs provoquées par le 3,4-benzpyrène (à 0,3%) sur la peau de la souris. Pour le confirmer, des expériences utilisant dix groupes de 30 souris femelles chacuns et huit concentrations croissantes de chloroacétone de 0,1 a 4,0%, n'ont pas montré de différences statistiquement significatives entre les groupes expérimentaux et celui du contrôle.
This work was supported by USPHS Grant CA-05431. 相似文献
This work was supported by USPHS Grant CA-05431. 相似文献
206.
Summary Mecamylamine and hexamethonium antagonize the prostration response of rats to centrally-administered nicotine; decamethonium and d-tubocurarine are less effective. Physostigmine does not elicit the response. Nicotine's central cholinergic effect thus may contribute to but does not fully account for its action.The authors thank the Public Health Service for its generous support of this project (grant No. 1 F32 NS 06334-01 NEUB). 相似文献
207.
Dinsdale EA Edwards RA Hall D Angly F Breitbart M Brulc JM Furlan M Desnues C Haynes M Li L McDaniel L Moran MA Nelson KE Nilsson C Olson R Paul J Brito BR Ruan Y Swan BK Stevens R Valentine DL Thurber RV Wegley L White BA Rohwer F 《Nature》2008,452(7187):629-632
Microbial activities shape the biogeochemistry of the planet and macroorganism health. Determining the metabolic processes performed by microbes is important both for understanding and for manipulating ecosystems (for example, disruption of key processes that lead to disease, conservation of environmental services, and so on). Describing microbial function is hampered by the inability to culture most microbes and by high levels of genomic plasticity. Metagenomic approaches analyse microbial communities to determine the metabolic processes that are important for growth and survival in any given environment. Here we conduct a metagenomic comparison of almost 15 million sequences from 45 distinct microbiomes and, for the first time, 42 distinct viromes and show that there are strongly discriminatory metabolic profiles across environments. Most of the functional diversity was maintained in all of the communities, but the relative occurrence of metabolisms varied, and the differences between metagenomes predicted the biogeochemical conditions of each environment. The magnitude of the microbial metabolic capabilities encoded by the viromes was extensive, suggesting that they serve as a repository for storing and sharing genes among their microbial hosts and influence global evolutionary and metabolic processes. 相似文献
208.
The Bicoid (Bcd) gradient in Drosophila has long been a model for the action of a morphogen in establishing embryonic polarity. However, it is now clear that bcd is a unique feature of higher Diptera. An evolutionarily ancient gene, orthodenticle (otd), has a bcd-like role in the beetle Tribolium. Unlike the Bcd gradient, which arises by diffusion of protein from an anteriorly localized messenger RNA, the Tribolium Otd gradient forms by translational repression of otd mRNA by a posteriorly localized factor. These differences in gradient formation are correlated with differences in modes of embryonic patterning. Drosophila uses long germ embryogenesis, where the embryo derives from the entire anterior-posterior axis, and all segments are patterned at the blastoderm stage, before gastrulation. In contrast, Tribolium undergoes short germ embryogenesis: the embryo arises from cells in the posterior of the egg, and only anterior segments are patterned at the blastoderm stage, with the remaining segments arising after gastrulation from a growth zone. Here we describe the role of otd in the long germband embryo of the wasp Nasonia vitripennis. We show that Nasonia otd maternal mRNA is localized at both poles of the embryo, and resulting protein gradients pattern both poles. Thus, localized Nasonia otd has two major roles that allow long germ development. It activates anterior targets at the anterior of the egg in a manner reminiscent of the Bcd gradient, and it is required for pre-gastrulation expression of posterior gap genes. 相似文献
209.
Wang J Soisson SM Young K Shoop W Kodali S Galgoci A Painter R Parthasarathy G Tang YS Cummings R Ha S Dorso K Motyl M Jayasuriya H Ondeyka J Herath K Zhang C Hernandez L Allocco J Basilio A Tormo JR Genilloud O Vicente F Pelaez F Colwell L Lee SH Michael B Felcetto T Gill C Silver LL Hermes JD Bartizal K Barrett J Schmatz D Becker JW Cully D Singh SB 《Nature》2006,441(7091):358-361
Bacterial infection remains a serious threat to human lives because of emerging resistance to existing antibiotics. Although the scientific community has avidly pursued the discovery of new antibiotics that interact with new targets, these efforts have met with limited success since the early 1960s. Here we report the discovery of platensimycin, a previously unknown class of antibiotics produced by Streptomyces platensis. Platensimycin demonstrates strong, broad-spectrum Gram-positive antibacterial activity by selectively inhibiting cellular lipid biosynthesis. We show that this anti-bacterial effect is exerted through the selective targeting of beta-ketoacyl-(acyl-carrier-protein (ACP)) synthase I/II (FabF/B) in the synthetic pathway of fatty acids. Direct binding assays show that platensimycin interacts specifically with the acyl-enzyme intermediate of the target protein, and X-ray crystallographic studies reveal that a specific conformational change that occurs on acylation must take place before the inhibitor can bind. Treatment with platensimycin eradicates Staphylococcus aureus infection in mice. Because of its unique mode of action, platensimycin shows no cross-resistance to other key antibiotic-resistant strains tested, including methicillin-resistant S. aureus, vancomycin-intermediate S. aureus and vancomycin-resistant enterococci. Platensimycin is the most potent inhibitor reported for the FabF/B condensing enzymes, and is the only inhibitor of these targets that shows broad-spectrum activity, in vivo efficacy and no observed toxicity. 相似文献