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排序方式: 共有185条查询结果,搜索用时 78 毫秒
171.
Transcriptional regulatory code of a eukaryotic genome 总被引:2,自引:0,他引:2
172.
Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells 总被引:2,自引:0,他引:2
Ito K Hirao A Arai F Matsuoka S Takubo K Hamaguchi I Nomiyama K Hosokawa K Sakurada K Nakagata N Ikeda Y Mak TW Suda T 《Nature》2004,431(7011):997-1002
The 'ataxia telangiectasia mutated' (Atm) gene maintains genomic stability by activating a key cell-cycle checkpoint in response to DNA damage, telomeric instability or oxidative stress. Mutational inactivation of the gene causes an autosomal recessive disorder, ataxia-telangiectasia, characterized by immunodeficiency, progressive cerebellar ataxia, oculocutaneous telangiectasia, defective spermatogenesis, premature ageing and a high incidence of lymphoma. Here we show that ATM has an essential function in the reconstitutive capacity of haematopoietic stem cells (HSCs) but is not as important for the proliferation or differentiation of progenitors, in a telomere-independent manner. Atm-/- mice older than 24 weeks showed progressive bone marrow failure resulting from a defect in HSC function that was associated with elevated reactive oxygen species. Treatment with anti-oxidative agents restored the reconstitutive capacity of Atm-/- HSCs, resulting in the prevention of bone marrow failure. Activation of the p16(INK4a)-retinoblastoma (Rb) gene product pathway in response to elevated reactive oxygen species led to the failure of Atm-/- HSCs. These results show that the self-renewal capacity of HSCs depends on ATM-mediated inhibition of oxidative stress. 相似文献
173.
174.
Stephens P Hunter C Bignell G Edkins S Davies H Teague J Stevens C O'Meara S Smith R Parker A Barthorpe A Blow M Brackenbury L Butler A Clarke O Cole J Dicks E Dike A Drozd A Edwards K Forbes S Foster R Gray K Greenman C Halliday K Hills K Kosmidou V Lugg R Menzies A Perry J Petty R Raine K Ratford L Shepherd R Small A Stephens Y Tofts C Varian J West S Widaa S Yates A Brasseur F Cooper CS Flanagan AM Knowles M Leung SY Louis DN Looijenga LH Malkowicz B Pierotti MA Teh B Chenevix-Trench G 《Nature》2004,431(7008):525-526
The protein-kinase family is the most frequently mutated gene family found in human cancer and faulty kinase enzymes are being investigated as promising targets for the design of antitumour therapies. We have sequenced the gene encoding the transmembrane protein tyrosine kinase ERBB2 (also known as HER2 or Neu) from 120 primary lung tumours and identified 4% that have mutations within the kinase domain; in the adenocarcinoma subtype of lung cancer, 10% of cases had mutations. ERBB2 inhibitors, which have so far proved to be ineffective in treating lung cancer, should now be clinically re-evaluated in the specific subset of patients with lung cancer whose tumours carry ERBB2 mutations. 相似文献
175.
Ken Udas 《Systemic Practice and Action Research》1997,10(5):509-532
In this paper Kurt Lewin's notions of conflict in social systems are applied to interprofessional social service and education
collaboratives. Interprofessional collaboration and service integration are parts of a larger reform effort addressed at reconfiguring
and rethinking the ways that social service and educational systems are designed, services are delivered, and professionals
are prepared. Constructs including privacy, cultural variance, group potency, need divergence, needs saturation, and tension
are related and discussed in terms of generic group-life and the interprofessional collaborative. The discussion points to
potential sources of tension and conflict in social systems and factors that may be influenced to reduce tension. 相似文献
176.
177.
Oceanography: anthropogenic carbon and ocean pH 总被引:9,自引:0,他引:9
178.
Nanog safeguards pluripotency and mediates germline development 总被引:3,自引:0,他引:3
Chambers I Silva J Colby D Nichols J Nijmeijer B Robertson M Vrana J Jones K Grotewold L Smith A 《Nature》2007,450(7173):1230-1234
179.
Burg TP Godin M Knudsen SM Shen W Carlson G Foster JS Babcock K Manalis SR 《Nature》2007,446(7139):1066-1069
Nanomechanical resonators enable the measurement of mass with extraordinary sensitivity. Previously, samples as light as 7 zeptograms (1 zg = 10(-21) g) have been weighed in vacuum, and proton-level resolution seems to be within reach. Resolving small mass changes requires the resonator to be light and to ring at a very pure tone-that is, with a high quality factor. In solution, viscosity severely degrades both of these characteristics, thus preventing many applications in nanotechnology and the life sciences where fluid is required. Although the resonant structure can be designed to minimize viscous loss, resolution is still substantially degraded when compared to measurements made in air or vacuum. An entirely different approach eliminates viscous damping by placing the solution inside a hollow resonator that is surrounded by vacuum. Here we demonstrate that suspended microchannel resonators can weigh single nanoparticles, single bacterial cells and sub-monolayers of adsorbed proteins in water with sub-femtogram resolution (1 Hz bandwidth). Central to these results is our observation that viscous loss due to the fluid is negligible compared to the intrinsic damping of our silicon crystal resonator. The combination of the low resonator mass (100 ng) and high quality factor (15,000) enables an improvement in mass resolution of six orders of magnitude over a high-end commercial quartz crystal microbalance. This gives access to intriguing applications, such as mass-based flow cytometry, the direct detection of pathogens, or the non-optical sizing and mass density measurement of colloidal particles. 相似文献
180.