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21.
Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor 总被引:72,自引:0,他引:72
Ohtaki T Shintani Y Honda S Matsumoto H Hori A Kanehashi K Terao Y Kumano S Takatsu Y Masuda Y Ishibashi Y Watanabe T Asada M Yamada T Suenaga M Kitada C Usuki S Kurokawa T Onda H Nishimura O Fujino M 《Nature》2001,411(6837):613-617
Metastasis is a major cause of death in cancer patients and involves a multistep process including detachment of cancer cells from a primary cancer, invasion of surrounding tissue, spread through circulation, re-invasion and proliferation in distant organs. KiSS-1 is a human metastasis suppressor gene, that suppresses metastases of human melanomas and breast carcinomas without affecting tumorigenicity. However, its gene product and functional mechanisms have not been elucidated. Here we show that KiSS-1 (refs 1, 4) encodes a carboxy-terminally amidated peptide with 54 amino-acid residues, which we have isolated from human placenta as the endogenous ligand of an orphan G-protein-coupled receptor (hOT7T175) and have named 'metastin'. Metastin inhibits chemotaxis and invasion of hOT7T175-transfected CHO cells in vitro and attenuates pulmonary metastasis of hOT7T175-transfected B16-BL6 melanomas in vivo. The results suggest possible mechanisms of action for KiSS-1 and a potential new therapeutic approach. 相似文献
22.
The Diels-Alder reaction, which forms a six-membered ring from an alkene (dienophile) and a 1,3-diene, is synthetically very useful for construction of cyclic products with high regio- and stereoselectivity under mild conditions. It has been applied to the synthesis of complex pharmaceutical and biologically active compounds. Although evidence on natural Diels-Alderases has been accumulated in the biosynthesis of secondary metabolites, there has been no report on the structural details of the natural Diels-Alderases. The function and catalytic mechanism of the natural Diels-Alderase are of great interest owing to the diversity of molecular skeletons in natural Diels-Alder adducts. Here we present the 1.70 A resolution crystal structure of the natural Diels-Alderase, fungal macrophomate synthase (MPS), in complex with pyruvate. The active site of the enzyme is large and hydrophobic, contributing amino acid residues that can hydrogen-bond to the substrate 2-pyrone. These data provide information on the catalytic mechanism of MPS, and suggest that the reaction proceeds via a large-scale structural reorganization of the product. 相似文献
23.
TRPV4 is a widely expressed cation channel of the 'transient receptor potential' (TRP) family that is related to the vanilloid receptor VR1 (TRPV1). It functions as a Ca2+ entry channel and displays remarkable gating promiscuity by responding to both physical stimuli (cell swelling, innoxious heat) and the synthetic ligand 4alphaPDD. An endogenous ligand for this channel has not yet been identified. Here we show that the endocannabinoid anandamide and its metabolite arachidonic acid activate TRPV4 in an indirect way involving the cytochrome P450 epoxygenase-dependent formation of epoxyeicosatrienoic acids. Application of 5',6'-epoxyeicosatrienoic acid at submicromolar concentrations activates TRPV4 in a membrane-delimited manner and causes Ca2+ influx through TRPV4-like channels in vascular endothelial cells. Activation of TRPV4 in vascular endothelial cells might therefore contribute to the relaxant effects of endocannabinoids and their P450 epoxygenase-dependent metabolites on vascular tone. 相似文献
24.
The S receptor kinase determines self-incompatibility in Brassica stigma 总被引:37,自引:0,他引:37
The self-incompatibility possessed by Brassica is an intraspecific reproductive barrier by which the stigma rejects self-pollen but accepts non-self-pollen for fertilization. The molecular/biochemical bases of recognition and rejection have been intensively studied. Self-incompatibility in Brassica is sporophytically controlled by the polymorphic S locus. Two tightly linked polymorphic genes at the S locus, S receptor kinase gene (SRK) and S locus glycoprotein gene (SLG), are specifically expressed in the papillar cells of the stigma, and analyses of self-compatible lines of Brassica have suggested that together they control stigma function in self-incompatibility interactions. Here we show, by transforming self-incompatible plants of Brassica rapa with an SRK28 and an SLG28 transgene separately, that expression of SRK28 alone, but not SLG28 alone, conferred the ability to reject self (S28)-pollen on the transgenic plants. We also show that the ability of SRK28 to reject S28 pollen was enhanced by SLG28. We conclude that SRK alone determines S haplotype specificity of the stigma, and that SLG acts to promote a full manifestation of the self-incompatibility response. 相似文献
25.
Microorganisms have flourished in the oceans since at least 3.8 billion years (3.8 Gyr) ago, but it is not at present clear when they first colonized the land. Organic matter in some Au/U-rich conglomerates and ancient soils of 2.3-2.7 Gyr age has been suggested as remnants of terrestrial organisms. Some 2.7-Gyr-old stromatolites have also been suggested as structures created by terrestrial organisms. However, it has been disputed whether this organic matter is indigenous or exogenic, and whether these stromatolites formed in marine or fresh water. Consequently, the oldest undisputed remnants of terrestrial organisms are currently the 1.2-Gyr-old microfossils from Arizona, USA. Unusually carbonaceous ancient soils--palaeosols--have been found in the Mpumalanga Province (Eastern Transvaal) of South Africa. Here we report the occurrences, elemental ratios (C, H, N, P) and isotopic compositions of this organic matter and its host rocks. These data show that the organic matter very probably represents remnants of microbial mats that developed on the soil surface between 2.6 and 2.7 Gyr ago. This places the development of terrestrial biomass more than 1.4 billion years earlier than previously reported. 相似文献
26.
ZHANG XianPing MA YanWei GAO ZhaoShun YU ZhengGuang WANG DongLiang WATANABE K GUO JianDong 《科学通报(英文版)》2007,52(18):2477-2480
Nano-SiC doped MgB2 tapes were prepared by the in situ powder-in-tube method. Heat treatment was performed at 650℃ for 1 h. XRD data indicate that SiC particles had reacted with the MgB2 during sintering process. MgB2 core seemed to be denser after SiC doping, and the critical temperature was slightly depressed. The critical current density Jc of the SiC doped tapes was significantly enhanced in magnetic fields up to 14 T compared to the undoped ones. For the 5% SiC doped samples, Jc was in- creased by a factor of 32 at 4.2 K, 10 T. The enhancement of Jc-B properties in SiC doped MgB2 tapes is considered to be due to the enhancement of grain linkages and the introduction of effective flux pining centers. The substitution of B by C in MgB2 grains is thought to be the main reason for the improve- ment of the flux pinning ability in SiC doped MgB2 tapes. 相似文献
27.
A rise in blood and liver acetaldehyde concentrations following ethanol loading (1.5 g/kg b.wt) was significantly reduced when rats were pretreated orally with taurine (0.5 g/kg), a potent in vitro activator of yeast aldehyde dehydrogenase. This taurine pretreatment produced a 4-fold increase in liver taurine content. 相似文献
28.
A radiation hybrid map of the rat genome containing 5,255 markers. 总被引:17,自引:0,他引:17
T K Watanabe M T Bihoreau L C McCarthy S L Kiguwa H Hishigaki A Tsuji J Browne Y Yamasaki A Mizoguchi-Miyakita K Oga T Ono S Okuno N Kanemoto E Takahashi K Tomita H Hayashi M Adachi C Webber M Davis S Kiel C Knights A Smith R Critcher J Miller T Thangarajah P J Day J R Hudson Y Irie T Takagi Y Nakamura P N Goodfellow G M Lathrop A Tanigami M R James 《Nature genetics》1999,22(1):27-36
A whole-genome radiation hybrid (RH) panel was used to construct a high-resolution map of the rat genome based on microsatellite and gene markers. These include 3,019 new microsatellite markers described here for the first time and 1,714 microsatellite markers with known genetic locations, allowing comparison and integration of maps from different sources. A robust RH framework map containing 1,030 positions ordered with odds of at least 1,000:1 has been defined as a tool for mapping these markers, and for future RH mapping in the rat. More than 500 genes which have been mapped in mouse and/or human were localized with respect to the rat RH framework, allowing the construction of detailed rat-mouse and rat-human comparative maps and illustrating the power of the RH approach for comparative mapping. 相似文献
29.
Administration of large dose of neostigmine caused very quickly marked myopathic changes at the motor end-plate region. With continued injections, however, some recovery of the structural features did occur suggesting the reconstructive changes in the affected regions. 相似文献
30.
The cleavage of dynorphin and three analogs containing paired basic residues by several proteases was investigated. The cysteine protease of neuroblastoma cells cleaved only the bond between Arg-Arg residues. Submandibular arginylendopeptidase, however, cleaved bonds between both Arg-Arg and Arg-Lys residues, and pancreatic trypsin at the carboxyl sides of both arginine and lysine residues. This shows that the cysteine protease is highly specific for paired arginine residues. 相似文献