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Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination 总被引:20,自引:0,他引:20
Otto EA Schermer B Obara T O'Toole JF Hiller KS Mueller AM Ruf RG Hoefele J Beekmann F Landau D Foreman JW Goodship JA Strachan T Kispert A Wolf MT Gagnadoux MF Nivet H Antignac C Walz G Drummond IA Benzing T Hildebrandt F 《Nature genetics》2003,34(4):413-420
Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, leads to chronic renal failure in children. The genes mutated in NPHP1 and NPHP4 have been identified, and a gene locus associated with infantile nephronophthisis (NPHP2) was mapped. The kidney phenotype of NPHP2 combines clinical features of NPHP and polycystic kidney disease (PKD). Here, we identify inversin (INVS) as the gene mutated in NPHP2 with and without situs inversus. We show molecular interaction of inversin with nephrocystin, the product of the gene mutated in NPHP1 and interaction of nephrocystin with beta-tubulin, a main component of primary cilia. We show that nephrocystin, inversin and beta-tubulin colocalize to primary cilia of renal tubular cells. Furthermore, we produce a PKD-like renal cystic phenotype and randomization of heart looping by knockdown of invs expression in zebrafish. The interaction and colocalization in cilia of inversin, nephrocystin and beta-tubulin connect pathogenetic aspects of NPHP to PKD, to primary cilia function and to left-right axis determination. 相似文献
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The on-going Three Gorges Project (TGP) aims to build one of the largest hydropower stations in the world. Previous investigations
have concluded that the reservoir is likely to induce medium-to-intense earthquakes. 23 GPS stations have been established
to maintain a geodetic and seismological monitoring network around the reservoir to monitor seismicity and crustal deformation,
and to facilitate mitigation activities in case an intense earthquake occurs. The velocity of GPS site was derived from 3
repeated GPS surveys. Meanwhile, another effort has been made to investigate the feasibility of application of satellite interferometric
synthetic aperture radar (InSAR) techniques in detecting crustal deformation possibly caused by impoundment of the Three Gorges
Reservoir. It has been made to derive digital elevation models (DEM) using European Remote Sensing (ERS) synthetic aperture
radar (SAR) imagery. Pairs of ERS SAR images in raw format are processed to generate digital elevation models. This effort
will help us evaluate the accuracy of the InSAR techniques for further derivation of background deformation patterns and future
detection of reservoir-induced crustal deformation in the area.
Foundation item: Supported by the Seismological Union Foundation of China (602015), NASA grant of US(NAG5-9065) and Key Project
of China Seismological Bureau(95-12-02)
Biography: Qiao Xue-jun(1968-), male, Associated professor, research direction: crustal deformation. 相似文献
76.
A conserved microRNA module exerts homeotic control over Petunia hybrida and Antirrhinum majus floral organ identity 总被引:3,自引:0,他引:3
Cartolano M Castillo R Efremova N Kuckenberg M Zethof J Gerats T Schwarz-Sommer Z Vandenbussche M 《Nature genetics》2007,39(7):901-905
It is commonly thought that deep phylogenetic conservation of plant microRNAs (miRNAs) and their targets indicates conserved regulatory functions. We show that the blind (bl) mutant of Petunia hybrida and the fistulata (fis) mutant of Antirrhinum majus, which have similar homeotic phenotypes, are recessive alleles of two homologous miRNA-encoding genes. The BL and FIS genes control the spatial restriction of homeotic class C genes to the inner floral whorls, but their ubiquitous early floral expression patterns are in contradiction with a potential role in patterning C gene expression. We provide genetic evidence for the unexpected function of the MIRFIS and MIRBL genes in the center of the flower and propose a dynamic mechanism underlying their regulatory role. Notably, Arabidopsis thaliana, a more distantly related species, also contains this miRNA module but does not seem to use it to confine early C gene expression to the center of the flower. 相似文献
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Zhu X Luke A Cooper RS Quertermous T Hanis C Mosley T Gu CC Tang H Rao DC Risch N Weder A 《Nature genetics》2005,37(2):177-181
Identification of genetic variants that contribute to risk of hypertension is challenging. As a complement to linkage and candidate gene association studies, we carried out admixture mapping using genome-scan microsatellite markers among the African American participants in the US National Heart, Lung, and Blood Institute's Family Blood Pressure Program. This population was assumed to have experienced recent admixture from ancestral groups originating in Africa and Europe. We used a set of unrelated individuals from Nigeria to represent the African ancestral population and used the European Americans in the Family Blood Pressure Program to provide estimates of allele frequencies for the European ancestors. We genotyped a common set of 269 microsatellite markers in the three groups at the same laboratory. The distribution of marker location-specific African ancestry, based on multipoint analysis, was shifted upward in hypertensive cases versus normotensive controls, consistent with linkage to genes conferring susceptibility. This shift was largely due to a small number of loci, including five adjacent markers on chromosome 6q and two on chromosome 21q. These results suggest that chromosome 6q24 and 21q21 may contain genes influencing risk of hypertension in African Americans. 相似文献
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