全文获取类型
收费全文 | 210篇 |
免费 | 0篇 |
国内免费 | 1篇 |
专业分类
系统科学 | 2篇 |
教育与普及 | 1篇 |
现状及发展 | 18篇 |
研究方法 | 55篇 |
综合类 | 128篇 |
自然研究 | 7篇 |
出版年
2016年 | 3篇 |
2015年 | 3篇 |
2014年 | 1篇 |
2013年 | 1篇 |
2012年 | 18篇 |
2011年 | 24篇 |
2010年 | 3篇 |
2009年 | 2篇 |
2008年 | 14篇 |
2007年 | 23篇 |
2006年 | 22篇 |
2005年 | 20篇 |
2004年 | 12篇 |
2003年 | 9篇 |
2002年 | 11篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1985年 | 2篇 |
1983年 | 2篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1974年 | 3篇 |
1973年 | 2篇 |
1971年 | 4篇 |
1970年 | 5篇 |
1969年 | 1篇 |
1967年 | 1篇 |
1965年 | 3篇 |
排序方式: 共有211条查询结果,搜索用时 0 毫秒
191.
192.
Scherer SE Muzny DM Buhay CJ Chen R Cree A Ding Y Dugan-Rocha S Gill R Gunaratne P Harris RA Hawes AC Hernandez J Hodgson AV Hume J Jackson A Khan ZM Kovar-Smith C Lewis LR Lozado RJ Metzker ML Milosavljevic A Miner GR Montgomery KT Morgan MB Nazareth LV Scott G Sodergren E Song XZ Steffen D Lovering RC Wheeler DA Worley KC Yuan Y Zhang Z Adams CQ Ansari-Lari MA Ayele M Brown MJ Chen G Chen Z Clerc-Blankenburg KP Davis C Delgado O Dinh HH Draper H Gonzalez-Garay ML Havlak P Jackson LR Jacob LS 《Nature》2006,440(7082):346-351
Human chromosome 12 contains more than 1,400 coding genes and 487 loci that have been directly implicated in human disease. The q arm of chromosome 12 contains one of the largest blocks of linkage disequilibrium found in the human genome. Here we present the finished sequence of human chromosome 12, which has been finished to high quality and spans approximately 132 megabases, representing approximately 4.5% of the human genome. Alignment of the human chromosome 12 sequence across vertebrates reveals the origin of individual segments in chicken, and a unique history of rearrangement through rodent and primate lineages. The rate of base substitutions in recent evolutionary history shows an overall slowing in hominids compared with primates and rodents. 相似文献
193.
Résumé Nous avons observé que l'injection de la 6-hydroxydopamine dans l'humeur vitrée des rats adaptés à la lumière bloquait le rétablissement de la sensibilité rétinale pendant l'adaptation à l'obscurité subséquente au traitement. Il est possible que cette observation soit une conséquence de la réaction du produit de l'oxydation de la 6-hydroxydopamine avec les groupes nucléophiliques de la rhodopsine.
This study was partially supported by Postdoctoral Training Grant No. MH 10965 to S.F.P. and by Eli Lilly Co., Research to Prevent Blindness, Inc., and NSF No. GB-39853 to L.T.G. Samples of 6-aminodopamine were kindly supplied by Drs.R. N. Adams (University of Kansas, Lawrence, Kansas) andE. L. Engelhardt (Merck Sharp and Dohme Res. Labs. West Point, Pa.) andp-quinone by Dr.P. A. Wehrli (Hoffmann-La Roche, Nutley, New Jersey). The authors thank Mr.L. Tomey for excellent technical assistance. 相似文献
This study was partially supported by Postdoctoral Training Grant No. MH 10965 to S.F.P. and by Eli Lilly Co., Research to Prevent Blindness, Inc., and NSF No. GB-39853 to L.T.G. Samples of 6-aminodopamine were kindly supplied by Drs.R. N. Adams (University of Kansas, Lawrence, Kansas) andE. L. Engelhardt (Merck Sharp and Dohme Res. Labs. West Point, Pa.) andp-quinone by Dr.P. A. Wehrli (Hoffmann-La Roche, Nutley, New Jersey). The authors thank Mr.L. Tomey for excellent technical assistance. 相似文献
194.
Identification and characterization of an inhibitor of haemopoietic stem cell proliferation 总被引:35,自引:0,他引:35
G J Graham E G Wright R Hewick S D Wolpe N M Wilkie D Donaldson S Lorimore I B Pragnell 《Nature》1990,344(6265):442-444
The haemopoietic system has three main compartments: multi-potential stem cells, intermediate stage progenitor cells and mature cells. The availability of simple reproducible culture systems has made possible the characterization and purification of regulators of the progenitor cells, including colony-stimulating factors and interleukins. In contrast, our knowledge of the regulators involved in the control of stem cell proliferation is limited. The steady-state quiescent status of the haemopoietic stem cell compartment is thought to be controlled by locally acting regulatory elements present in the stromal microenvironment, but their purification has been hampered by the lack of suitable culture systems. We have recently developed a novel in vitro colony assay that detects a primitive cell (CFU-A) which has similar proliferative characteristics, in normal and regenerating bone marrow, to the CFU-S (haemopoietic stem cells, as defined by the spleen colony assay) and which responds to CFU-S-specific proliferation regulators. We have now used this assay to purify to homogeneity a macrophage-derived reversible inhibitor of haemopoietic stem cell proliferation (stem cell inhibitor, SCI). Antibody inhibition and sequence data indicate that SCI is identical to a previously described cytokine, macrophage inflammatory protein-1 alpha (MIP-1 alpha), and that SCI/MIP-1 alpha is functionally and antigenically identical to the CFU-S inhibitory activity obtained from primary cultures of normal bone marrow cells. The biological activities of SCI/MIP-1 alpha suggest that it is a primary negative regulator of stem cell proliferation and that it has important therapeutic applications in protecting haemopoietic stem cells from damage during cytotoxic therapies for cancer. 相似文献
195.
Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9 总被引:21,自引:0,他引:21
The low-density lipoprotein receptor (LDLR) prevents hypercholesterolemia and atherosclerosis by removing low-density lipoprotein (LDL) from circulation. Mutations in the genes encoding either LDLR or its ligand (APOB) cause severe hypercholesterolemia. Missense mutations in PCSK9, encoding a serine protease in the secretory pathway, also cause hypercholesterolemia. These mutations are probably gain-of-function mutations, as overexpression of PCSK9 in the liver of mice produces hypercholesterolemia by reducing LDLR number. To test whether loss-of-function mutations in PCSK9 have the opposite effect, we sequenced the coding region of PCSK9 in 128 subjects (50% African American) with low plasma levels of LDL and found two nonsense mutations (Y142X and C679X). These mutations were common in African Americans (combined frequency, 2%) but rare in European Americans (<0.1%) and were associated with a 40% reduction in plasma levels of LDL cholesterol. These data indicate that common sequence variations have large effects on plasma cholesterol levels in selected populations. 相似文献
196.
Stephens P Edkins S Davies H Greenman C Cox C Hunter C Bignell G Teague J Smith R Stevens C O'Meara S Parker A Tarpey P Avis T Barthorpe A Brackenbury L Buck G Butler A Clements J Cole J Dicks E Edwards K Forbes S Gorton M Gray K Halliday K Harrison R Hills K Hinton J Jones D Kosmidou V Laman R Lugg R Menzies A Perry J Petty R Raine K Shepherd R Small A Solomon H Stephens Y Tofts C Varian J Webb A West S Widaa S Yates A Brasseur F Cooper CS Flanagan AM Green A Knowles M Leung SY Looijenga LH 《Nature genetics》2005,37(6):590-592
We examined the coding sequence of 518 protein kinases, approximately 1.3 Mb of DNA per sample, in 25 breast cancers. In many tumors, we detected no somatic mutations. But a few had numerous somatic mutations with distinctive patterns indicative of either a mutator phenotype or a past exposure. 相似文献
197.
Golgi biogenesis in Toxoplasma gondii 总被引:7,自引:0,他引:7
Pelletier L Stern CA Pypaert M Sheff D Ngô HM Roper N He CY Hu K Toomre D Coppens I Roos DS Joiner KA Warren G 《Nature》2002,418(6897):548-552
Two models have been put forward to explain the growth of new Golgi during the cell cycle. The first suggests that a new Golgi grows out of the endoplasmic reticulum by de novo synthesis. The second suggests that a pre-existing Golgi is needed for the growth of a new one, that is, the Golgi is an autonomously replicating organelle. To resolve this issue, we have exploited the simplicity of the apicomplexan parasite Toxoplasma gondii, which has only a single Golgi stack. Here we show, by using video fluorescence microscopy and three-dimensional reconstructions of serial thin sections, that the Golgi grows by a process of lateral extension followed by medial fission. Further fission leads to the inheritance by each daughter of a pair of Golgi structures, which then coalesce to re-form a single Golgi. Our results indicate that new Golgi grow by autonomous duplication and raise the possibility that the Golgi is a paired structure that is analogous to centrioles. 相似文献
198.
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
199.
200.
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