全文获取类型
收费全文 | 58篇 |
免费 | 0篇 |
专业分类
现状及发展 | 15篇 |
研究方法 | 5篇 |
综合类 | 37篇 |
自然研究 | 1篇 |
出版年
2016年 | 1篇 |
2015年 | 1篇 |
2012年 | 1篇 |
2011年 | 1篇 |
2010年 | 1篇 |
2008年 | 2篇 |
2007年 | 2篇 |
2006年 | 6篇 |
2005年 | 3篇 |
2004年 | 3篇 |
2003年 | 4篇 |
2002年 | 2篇 |
2001年 | 2篇 |
2000年 | 2篇 |
1989年 | 1篇 |
1987年 | 2篇 |
1986年 | 5篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1980年 | 1篇 |
1978年 | 2篇 |
1976年 | 1篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1970年 | 1篇 |
排序方式: 共有58条查询结果,搜索用时 37 毫秒
1.
Nras loss induces metastatic conversion of Rb1-deficient neuroendocrine thyroid tumor 总被引:2,自引:0,他引:2
Takahashi C Contreras B Iwanaga T Takegami Y Bakker A Bronson RT Noda M Loda M Hunt JL Ewen ME 《Nature genetics》2006,38(1):118-123
Mutations in the gene encoding the retinoblastoma tumor suppressor predispose humans and mice to tumor development. Here we have assessed the effect of Nras loss on tumor development in Rb1 heterozygous mice. Loss of one or two Nras alleles is shown to significantly reduce the severity of pituitary tumors arising in Rb1(+/-) animals by enhancing their differentiation. By contrast, C-cell thyroid adenomas occurring in Rb1(+/-) mice progress to metastatic medullary carcinomas after loss of Nras. In Rb1(+/-)Nras(+/-) animals, distant medullary thyroid carcinoma metastases are associated with loss of the remaining wild-type Nras allele. Loss of Nras in Rb1-deficient C cells results in elevated Ras homolog family A (RhoA) activity, and this is causally linked to the invasiveness and metastatic behavior of these cells. These findings suggest that the loss of the proto-oncogene Nras in certain cellular contexts can promote malignant tumor progression. 相似文献
2.
Spatial asymmetries in neural connectivity have an important role in creating basic building blocks of neuronal processing. A key circuit module of directionally selective (DS) retinal ganglion cells is a spatially asymmetric inhibitory input from starburst amacrine cells. It is not known how and when this circuit asymmetry is established during development. Here we photostimulate mouse starburst cells targeted with channelrhodopsin-2 (refs 6-8) while recording from a single genetically labelled type of DS cell. We follow the spatial distribution of synaptic strengths between starburst and DS cells during early postnatal development before these neurons can respond to a physiological light stimulus, and confirm connectivity by monosynaptically restricted trans-synaptic rabies viral tracing. We show that asymmetry develops rapidly over a 2-day period through an intermediate state in which random or symmetric synaptic connections have been established. The development of asymmetry involves the spatially selective reorganization of inhibitory synaptic inputs. Intriguingly, the spatial distribution of excitatory synaptic inputs from starburst cells is significantly more symmetric than that of the inhibitory inputs at the end of this developmental period. Our work demonstrates a rapid developmental switch from a symmetric to asymmetric input distribution for inhibition in the neural circuit of a principal cell. 相似文献
3.
Hulpke S Tomioka M Kremmer E Ueda K Abele R Tampé R 《Cellular and molecular life sciences : CMLS》2012,69(19):3317-3327
The loading of antigenic peptides onto major histocompatibility complex class I (MHC I) molecules is an essential step in the adaptive immune response against virally or malignantly transformed cells. The ER-resident peptide-loading complex (PLC) consists of the transporter associated with antigen processing (TAP1 and TAP2), assembled with the auxiliary factors tapasin and MHC I. Here, we demonstrated that the N-terminal extension of each TAP subunit represents an autonomous domain, named TMD(0), which is correctly targeted to and inserted into the ER membrane. In the absence of coreTAP, each TMD(0) recruits tapasin in a 1:1 stoichiometry. Although the TMD(0)s lack known ER retention/retrieval signals, they are localized to the ER membrane even in tapasin-deficient cells. We conclude that the TMD(0)s of TAP form autonomous interaction hubs linking antigen translocation into the ER with peptide loading onto MHC I, hence ensuring a major function in the integrity of the antigen-processing machinery. 相似文献
4.
The genome sequence and structure of rice chromosome 1 总被引:2,自引:0,他引:2
Sasaki T Matsumoto T Yamamoto K Sakata K Baba T Katayose Y Wu J Niimura Y Cheng Z Nagamura Y Antonio BA Kanamori H Hosokawa S Masukawa M Arikawa K Chiden Y Hayashi M Okamoto M Ando T Aoki H Arita K Hamada M Harada C Hijishita S Honda M Ichikawa Y Idonuma A Iijima M Ikeda M Ikeno M Ito S Ito T Ito Y Ito Y Iwabuchi A Kamiya K Karasawa W Katagiri S Kikuta A Kobayashi N Kono I Machita K Maehara T Mizuno H Mizubayashi T Mukai Y Nagasaki H Nakashima M Nakama Y Nakamichi Y Nakamura M Namiki N 《Nature》2002,420(6913):312-316
The rice species Oryza sativa is considered to be a model plant because of its small genome size, extensive genetic map, relative ease of transformation and synteny with other cereal crops. Here we report the essentially complete sequence of chromosome 1, the longest chromosome in the rice genome. We summarize characteristics of the chromosome structure and the biological insight gained from the sequence. The analysis of 43.3 megabases (Mb) of non-overlapping sequence reveals 6,756 protein coding genes, of which 3,161 show homology to proteins of Arabidopsis thaliana, another model plant. About 30% (2,073) of the genes have been functionally categorized. Rice chromosome 1 is (G + C)-rich, especially in its coding regions, and is characterized by several gene families that are dispersed or arranged in tandem repeats. Comparison with a draft sequence indicates the importance of a high-quality finished sequence. 相似文献
5.
6.
T. Suga T. Hirata M. Noda T. Matsuura 《Cellular and molecular life sciences : CMLS》1970,26(11):1192-1193
Zusammenfassung Die Reaktion von (-)-2-Hydroxypinocamphon (I) mit wasserfreier Oxalsäure in Aceton liefert (-)-Dihydro--campholenolakton (IIa). Die Stereochemie liess sich durch NMR-, ORD- und CD-Spektren bestimmen. Es wird ein Reaktionsmechanismus diskutiert. 相似文献
7.
SWAP-70 is a guanine-nucleotide-exchange factor that mediates signalling of membrane ruffling 总被引:9,自引:0,他引:9
Shinohara M Terada Y Iwamatsu A Shinohara A Mochizuki N Higuchi M Gotoh Y Ihara S Nagata S Itoh H Fukui Y Jessberger R 《Nature》2002,416(6882):759-763
Phosphoinositide-3-OH kinase (PI(3)K), activated through growth factor stimulation, generates a lipid second messenger, phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3). PtdIns(3,4,5)P3 is instrumental in signalling pathways that trigger cell activation, cytoskeletal rearrangement, survival and other reactions. However, some targets of PtdIns(3,4,5)P3 are yet to be discovered. We demonstrate that SWAP-70, a unique signalling protein, specifically binds PtdIns(3,4,5)P3. On stimulation by growth factors, cytoplasmic SWAP-70, which is dependent on PI(3)K but independent of Ras, moved to cell membrane rearrangements known as ruffles. However, mutant SWAP-70 lacking the ability to bind PtdIns(3,4,5)P3 blocked membrane ruffling induced by epidermal growth factor or platelet-derived growth factor. SWAP-70 shows low homology with Rac-guanine nucleotide exchange factors (GEFs), and catalyses PtdIns(3,4,5)P3-dependent guanine nucleotide exchange to Rac. SWAP-70-deficient fibroblasts showed impaired membrane ruffling after stimulation with epidermal growth factor, and failed to activate Rac fully. We conclude that SWAP-70 is a new type of Rac-GEF which, independently of Ras, transduces signals from tyrosine kinase receptors to Rac. 相似文献
8.
Evidence for ubiquitous strong electron-phonon coupling in high-temperature superconductors 总被引:3,自引:0,他引:3
Lanzara A Bogdanov PV Zhou XJ Kellar SA Feng DL Lu ED Yoshida T Eisaki H Fujimori A Kishio K Shimoyama JI Noda T Uchida S Hussain Z Shen ZX 《Nature》2001,412(6846):510-514
Coupling between electrons and phonons (lattice vibrations) drives the formation of the electron pairs responsible for conventional superconductivity. The lack of direct evidence for electron-phonon coupling in the electron dynamics of the high-transition-temperature superconductors has driven an intensive search for an alternative mechanism. A coupling of an electron with a phonon would result in an abrupt change of its velocity and scattering rate near the phonon energy. Here we use angle-resolved photoemission spectroscopy to probe electron dynamics-velocity and scattering rate-for three different families of copper oxide superconductors. We see in all of these materials an abrupt change of electron velocity at 50-80 meV, which we cannot explain by any known process other than to invoke coupling with the phonons associated with the movement of the oxygen atoms. This suggests that electron-phonon coupling strongly influences the electron dynamics in the high-temperature superconductors, and must therefore be included in any microscopic theory of superconductivity. 相似文献
9.
High-Q photonic nanocavity in a two-dimensional photonic crystal 总被引:1,自引:0,他引:1
Photonic cavities that strongly confine light are finding applications in many areas of physics and engineering, including coherent electron-photon interactions, ultra-small filters, low-threshold lasers, photonic chips, nonlinear optics and quantum information processing. Critical for these applications is the realization of a cavity with both high quality factor, Q, and small modal volume, V. The ratio Q/V determines the strength of the various cavity interactions, and an ultra-small cavity enables large-scale integration and single-mode operation for a broad range of wavelengths. However, a high-Q cavity of optical wavelength size is difficult to fabricate, as radiation loss increases in inverse proportion to cavity size. With the exception of a few recent theoretical studies, definitive theories and experiments for creating high-Q nanocavities have not been extensively investigated. Here we use a silicon-based two-dimensional photonic-crystal slab to fabricate a nanocavity with Q = 45,000 and V = 7.0 x 10(-14) cm3; the value of Q/V is 10-100 times larger than in previous studies. Underlying this development is the realization that light should be confined gently in order to be confined strongly. Integration with other photonic elements is straightforward, and a large free spectral range of 100 nm has been demonstrated. 相似文献
10.
Cloning, sequencing and expression of cDNA for a novel subunit of acetylcholine receptor from calf muscle 总被引:5,自引:0,他引:5
T Takai M Noda M Mishina S Shimizu Y Furutani T Kayano T Ikeda T Kubo H Takahashi T Takahashi 《Nature》1985,315(6022):761-764
The nicotinic acetylcholine receptor (AChR) from fish electric organ has a subunit structure of alpha 2 beta gamma delta, and this is thought to be also the case for the mammalian skeletal muscle AChR. By cloning and sequencing the complementary or genomic DNAs, we have previously elucidated the primary structures of all four subunits of the Torpedo californica electroplax and calf muscle AChR and of the alpha- and gamma-subunits of the human muscle AChR; the primary structures of the gamma-subunit of the T. californica AChR and the alpha-subunit of the Torpedo marmorata AChR have also been deduced elsewhere. We have now cloned DNA complementary to the calf muscle messenger RNA encoding a novel polypeptide (the epsilon-subunit) whose deduced amino-acid sequence has features characteristic of the AChR subunits and which shows higher sequence homology with the gamma-subunit than with the other subunits. cDNA expression studies indicate that the calf epsilon-subunit, as well as the calf gamma-subunit, can replace the Torpedo gamma-subunit to form the functional receptor in combination with the Torpedo alpha-, beta- and delta-subunits. 相似文献