全文获取类型
收费全文 | 190篇 |
免费 | 0篇 |
国内免费 | 1篇 |
专业分类
系统科学 | 1篇 |
现状及发展 | 37篇 |
研究方法 | 44篇 |
综合类 | 108篇 |
自然研究 | 1篇 |
出版年
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 2篇 |
2014年 | 2篇 |
2013年 | 1篇 |
2012年 | 19篇 |
2011年 | 10篇 |
2010年 | 6篇 |
2009年 | 2篇 |
2008年 | 6篇 |
2007年 | 12篇 |
2006年 | 10篇 |
2005年 | 9篇 |
2004年 | 9篇 |
2003年 | 9篇 |
2002年 | 14篇 |
2001年 | 3篇 |
2000年 | 4篇 |
1999年 | 6篇 |
1997年 | 1篇 |
1995年 | 1篇 |
1992年 | 4篇 |
1990年 | 1篇 |
1989年 | 4篇 |
1987年 | 1篇 |
1984年 | 2篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 5篇 |
1979年 | 2篇 |
1978年 | 4篇 |
1977年 | 5篇 |
1976年 | 4篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1973年 | 3篇 |
1971年 | 2篇 |
1970年 | 4篇 |
1969年 | 1篇 |
1968年 | 2篇 |
1966年 | 2篇 |
1965年 | 2篇 |
1964年 | 2篇 |
1957年 | 3篇 |
排序方式: 共有191条查询结果,搜索用时 0 毫秒
41.
Bentley DR Balasubramanian S Swerdlow HP Smith GP Milton J Brown CG Hall KP Evers DJ Barnes CL Bignell HR Boutell JM Bryant J Carter RJ Keira Cheetham R Cox AJ Ellis DJ Flatbush MR Gormley NA Humphray SJ Irving LJ Karbelashvili MS Kirk SM Li H Liu X Maisinger KS Murray LJ Obradovic B Ost T Parkinson ML Pratt MR Rasolonjatovo IM Reed MT Rigatti R Rodighiero C Ross MT Sabot A Sankar SV Scally A Schroth GP Smith ME Smith VP Spiridou A Torrance PE Tzonev SS Vermaas EH Walter K Wu X Zhang L Alam MD 《Nature》2008,456(7218):53-59
DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long (400-800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re-sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation. Here we report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost. Single molecules of DNA are attached to a flat surface, amplified in situ and used as templates for synthetic sequencing with fluorescent reversible terminator deoxyribonucleotides. Images of the surface are analysed to generate high-quality sequence. We demonstrate application of this approach to human genome sequencing on flow-sorted X chromosomes and then scale the approach to determine the genome sequence of a male Yoruba from Ibadan, Nigeria. We build an accurate consensus sequence from >30x average depth of paired 35-base reads. We characterize four million single-nucleotide polymorphisms and four hundred thousand structural variants, many of which were previously unknown. Our approach is effective for accurate, rapid and economical whole-genome re-sequencing and many other biomedical applications. 相似文献
42.
Influence of ethanol on calcium, inositol phospholipids and intracellular signalling mechanisms 总被引:1,自引:0,他引:1
Studies have implicated Ca++ in the actions of ethanol at many biochemical levels. Calcium as a major intracellular messenger in the central nervous system is involved in many processes, including protein phosphorylation enzyme activation and secretion of hormones and neurotransmitters. The control of intracellular calcium, therefore, represents a major step by which neuronal cells regulate their activities. The present review focuses on three primary areas which influence intracellular calcium levels; voltage-dependent Ca++ channels, receptor-mediated inositol phospholipid hydrolysis, and Ca++/Mg++-ATPase, the high affinity membrane Ca++ pump. Current research suggests that a subtype of the voltage-dependent Ca++ channel, the dihydropyridine-sensitive Ca++ channel, is uniquely sensitive to acute and chronic ethanol treatment. Acute exposure inhibits, while chronic ethanol exposure increases 45Ca++-influx and [3H]dihydropyridine receptor binding sites. In addition, acute and chronic exposure to ethanol inhibits, then increases Ca++/Mg++-ATPase activity in neuronal membranes. Changes in Ca++ channel and Ca++/Mg++-ATPase activity following chronic ethanol may occur as an adaptation process to increase Ca++ availability for intracellular processes. Since receptor-dependent inositol phospholipid hydrolysis is enhanced after chronic ethanol treatment, subsequent activation of protein kinase-C may also be involved in the adaptation process and may indicate increased coupling for receptor-dependent changes in Ca++/Mg++-ATPase activity. The increased sensitivity of three Ca++-dependent processes suggest that adaptation to chronic ethanol exposure may involve coupling of one or more of these processes to receptor-mediated events. 相似文献
43.
44.
45.
Traditional models of the supercontinent cycle predict that the next supercontinent--'Amasia'--will form either where Pangaea rifted (the 'introversion' model) or on the opposite side of the world (the 'extroversion' models). Here, by contrast, we develop an 'orthoversion' model whereby a succeeding supercontinent forms 90° away, within the great circle of subduction encircling its relict predecessor. A supercontinent aggregates over a mantle downwelling but then influences global-scale mantle convection to create an upwelling under the landmass. We calculate the minimum moment of inertia about which oscillatory true polar wander occurs owing to the prolate shape of the non-hydrostatic Earth. By fitting great circles to each supercontinent's true polar wander legacy, we determine that the arc distances between successive supercontinent centres (the axes of the respective minimum moments of inertia) are 88° for Nuna to Rodinia and 87° for Rodinia to Pangaea--as predicted by the orthoversion model. Supercontinent centres can be located back into Precambrian time, providing fixed points for the calculation of absolute palaeolongitude over billion-year timescales. Palaeogeographic reconstructions additionally constrained in palaeolongitude will provide increasingly accurate estimates of ancient plate motions and palaeobiogeographic affinities. 相似文献
46.
Zhang J Grindley JC Yin T Jayasinghe S He XC Ross JT Haug JS Rupp D Porter-Westpfahl KS Wiedemann LM Wu H Li L 《Nature》2006,441(7092):518-522
Haematopoietic stem cells (HSCs) must achieve a balance between quiescence and activation that fulfils immediate demands for haematopoiesis without compromising long-term stem cell maintenance, yet little is known about the molecular events governing this balance. Phosphatase and tensin homologue (PTEN) functions as a negative regulator of the phosphatidylinositol-3-OH kinase (PI(3)K)-Akt pathway, which has crucial roles in cell proliferation, survival, differentiation and migration. Here we show that inactivation of PTEN in bone marrow HSCs causes their short-term expansion, but long-term decline, primarily owing to an enhanced level of HSC activation. PTEN-deficient HSCs engraft normally in recipient mice, but have an impaired ability to sustain haematopoietic reconstitution, reflecting the dysregulation of their cell cycle and decreased retention in the bone marrow niche. Mice with PTEN-mutant bone marrow also have an increased representation of myeloid and T-lymphoid lineages and develop myeloproliferative disorder (MPD). Notably, the cell populations that expand in PTEN mutants match those that become dominant in the acute myeloid/lymphoid leukaemia that develops in the later stages of MPD. Thus, PTEN has essential roles in restricting the activation of HSCs, in lineage fate determination, and in the prevention of leukaemogenesis. 相似文献
47.
48.
Genome sequence of Bacillus cereus and comparative analysis with Bacillus anthracis 总被引:10,自引:0,他引:10
Ivanova N Sorokin A Anderson I Galleron N Candelon B Kapatral V Bhattacharyya A Reznik G Mikhailova N Lapidus A Chu L Mazur M Goltsman E Larsen N D'Souza M Walunas T Grechkin Y Pusch G Haselkorn R Fonstein M Ehrlich SD Overbeek R Kyrpides N 《Nature》2003,423(6935):87-91
Bacillus cereus is an opportunistic pathogen causing food poisoning manifested by diarrhoeal or emetic syndromes. It is closely related to the animal and human pathogen Bacillus anthracis and the insect pathogen Bacillus thuringiensis, the former being used as a biological weapon and the latter as a pesticide. B. anthracis and B. thuringiensis are readily distinguished from B. cereus by the presence of plasmid-borne specific toxins (B. anthracis and B. thuringiensis) and capsule (B. anthracis). But phylogenetic studies based on the analysis of chromosomal genes bring controversial results, and it is unclear whether B. cereus, B. anthracis and B. thuringiensis are varieties of the same species or different species. Here we report the sequencing and analysis of the type strain B. cereus ATCC 14579. The complete genome sequence of B. cereus ATCC 14579 together with the gapped genome of B. anthracis A2012 enables us to perform comparative analysis, and hence to identify the genes that are conserved between B. cereus and B. anthracis, and the genes that are unique for each species. We use the former to clarify the phylogeny of the cereus group, and the latter to determine plasmid-independent species-specific markers. 相似文献
49.
50.
Whole-genome sequence of Schistosoma haematobium 总被引:1,自引:0,他引:1
Young ND Jex AR Li B Liu S Yang L Xiong Z Li Y Cantacessi C Hall RS Xu X Chen F Wu X Zerlotini A Oliveira G Hofmann A Zhang G Fang X Kang Y Campbell BE Loukas A Ranganathan S Rollinson D Rinaldi G Brindley PJ Yang H Wang J Wang J Gasser RB 《Nature genetics》2012,44(2):221-225
Schistosomiasis is a neglected tropical disease caused by blood flukes (genus Schistosoma; schistosomes) and affecting 200 million people worldwide. No vaccines are available, and treatment relies on one drug, praziquantel. Schistosoma haematobium has come into the spotlight as a major cause of urogenital disease, as an agent linked to bladder cancer and as a predisposing factor for HIV/AIDS. The parasite is transmitted to humans from freshwater snails. Worms dwell in blood vessels and release eggs that become embedded in the bladder wall to elicit chronic immune-mediated disease and induce squamous cell carcinoma. Here we sequenced the 385-Mb genome of S. haematobium using Illumina-based technology at 74-fold coverage and compared it to sequences from related parasites. We included genome annotation based on function, gene ontology, networking and pathway mapping. This genome now provides an unprecedented resource for many fundamental research areas and shows great promise for the design of new disease interventions. 相似文献