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排序方式: 共有103条查询结果,搜索用时 31 毫秒
1.
Young DA Wright AP Roberts JL Warner RC Young NW Greenbaum JS Schroeder DM Holt JW Sugden DE Blankenship DD van Ommen TD Siegert MJ 《Nature》2011,474(7349):72-75
The first Cenozoic ice sheets initiated in Antarctica from the Gamburtsev Subglacial Mountains and other highlands as a result of rapid global cooling ~34 million years ago. In the subsequent 20 million years, at a time of declining atmospheric carbon dioxide concentrations and an evolving Antarctic circumpolar current, sedimentary sequence interpretation and numerical modelling suggest that cyclical periods of ice-sheet expansion to the continental margin, followed by retreat to the subglacial highlands, occurred up to thirty times. These fluctuations were paced by orbital changes and were a major influence on global sea levels. Ice-sheet models show that the nature of such oscillations is critically dependent on the pattern and extent of Antarctic topographic lowlands. Here we show that the basal topography of the Aurora Subglacial Basin of East Antarctica, at present overlain by 2-4.5?km of ice, is characterized by a series of well-defined topographic channels within a mountain block landscape. The identification of this fjord landscape, based on new data from ice-penetrating radar, provides an improved understanding of the topography of the Aurora Subglacial Basin and its surroundings, and reveals a complex surface sculpted by a succession of ice-sheet configurations substantially different from today's. At different stages during its fluctuations, the edge of the East Antarctic Ice Sheet lay pinned along the margins of the Aurora Subglacial Basin, the upland boundaries of which are currently above sea level and the deepest parts of which are more than 1?km below sea level. Although the timing of the channel incision remains uncertain, our results suggest that the fjord landscape was carved by at least two iceflow regimes of different scales and directions, each of which would have over-deepened existing topographic depressions, reversing valley floor slopes. 相似文献
2.
Kao WH Klag MJ Meoni LA Reich D Berthier-Schaad Y Li M Coresh J Patterson N Tandon A Powe NR Fink NE Sadler JH Weir MR Abboud HE Adler SG Divers J Iyengar SK Freedman BI Kimmel PL Knowler WC Kohn OF Kramp K Leehey DJ Nicholas SB Pahl MV Schelling JR Sedor JR Thornley-Brown D Winkler CA Smith MW Parekh RS;Family Investigation of Nephropathy Diabetes Research Group 《Nature genetics》2008,40(10):1185-1192
As end-stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans, we hypothesized that susceptibility alleles for ESRD have a higher frequency in the West African than the European gene pool. We carried out a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and found a highly significant association between excess African ancestry and nondiabetic ESRD (lod score = 5.70) but not diabetic ESRD (lod = 0.47) on chromosome 22q12. Each copy of the European ancestral allele conferred a relative risk of 0.50 (95% CI = 0.39-0.63) compared to African ancestry. Multiple common SNPs (allele frequencies ranging from 0.2 to 0.6) in the gene encoding nonmuscle myosin heavy chain type II isoform A (MYH9) were associated with two to four times greater risk of nondiabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans. 相似文献
3.
PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans
Grall A Guaguère E Planchais S Grond S Bourrat E Hausser I Hitte C Le Gallo M Derbois C Kim GJ Lagoutte L Degorce-Rubiales F Radner FP Thomas A Küry S Bensignor E Fontaine J Pin D Zimmermann R Zechner R Lathrop M Galibert F André C Fischer J 《Nature genetics》2012,44(2):140-147
Ichthyoses comprise a heterogeneous group of genodermatoses characterized by abnormal desquamation over the whole body, for which the genetic causes of several human forms remain unknown. We used a spontaneous dog model in the golden retriever breed, which is affected by a lamellar ichthyosis resembling human autosomal recessive congenital ichthyoses (ARCI), to carry out a genome-wide association study. We identified a homozygous insertion-deletion (indel) mutation in PNPLA1 that leads to a premature stop codon in all affected golden retriever dogs. We subsequently found one missense and one nonsense mutation in the catalytic domain of human PNPLA1 in six individuals with ARCI from two families. Further experiments highlighted the importance of PNPLA1 in the formation of the epidermal lipid barrier. This study identifies a new gene involved in human ichthyoses and provides insights into the localization and function of this yet uncharacterized member of the PNPLA protein family. 相似文献
4.
Dobbins SE Broderick P Melin B Feychting M Johansen C Andersson U Brännström T Schramm J Olver B Lloyd A Ma YP Hosking FJ Lönn S Ahlbom A Henriksson R Schoemaker MJ Hepworth SJ Hoffmann P Mühleisen TW Nöthen MM Moebus S Eisele L Kosteljanetz M Muir K Swerdlow A Simon M Houlston RS 《Nature genetics》2011,43(9):825-827
To identify susceptibility loci for meningioma, we conducted a genome-wide association study of 859 affected individuals (cases) and 704 controls with validation in two independent sample sets totaling 774 cases and 1,764 controls. We identified a new susceptibility locus for meningioma at 10p12.31 (MLLT10, rs11012732, odds ratio = 1.46, P(combined) = 1.88 × 10(-14)). This finding advances our understanding of the genetic basis of meningioma development. 相似文献
5.
Ann-Karin Haas Gunnar Kleinau Inna Hoyer Susanne Neumann Jens Furkert Claudia Rutz Ralf Schülein Marvin C. Gershengorn Gerd Krause 《Cellular and molecular life sciences : CMLS》2011,68(1):159-167
The thyrotropin receptor (TSHR) exhibits elevated cAMP signaling in the basal state and becomes fully activated by thyrotropin.
Previously we presented evidence that small-molecule ligands act allosterically within the transmembrane region in contrast
to the orthosteric extracellular hormone-binding sites. Our goal in this study was to identify positions that surround the
allosteric pocket and that are sensitive for inactivation of TSHR. Homology modeling combined with site-directed mutagenesis
and functional characterization revealed seven mutants located in the allosteric binding site that led to a decrease of basal
cAMP signaling activity. The majority of these silencing mutations, which constrain the TSHR in an inactive conformation,
are found in two clusters when mapped onto the 3D structural model. We suggest that the amino acid positions identified herein
are indicating locations where small-molecule antagonists, both neutral antagonists and inverse agonists, might interfere
with active TSHR conformations. 相似文献
6.
T. Schroeder D. D. Avery H. A. Cross 《Cellular and molecular life sciences : CMLS》1972,28(8):923-924
Résumé On a donné à 96 rats mâles albinos six doses différentes de plomb tétra-éthyle par intubation intragastrique. Une courbe dose-réaction a été établie à partir des résultats obtenus et les calculs ont donné une valeur LD50 de 12,3 mg/kg (11,50 à 13,15). Cette valeur diffère de celle qui a été obtenue précédemment. On croit que cette différence résulte du fait qu'un nombre plus grand d'échantillons a été utilisé dans cette série d'observations. 相似文献
7.
High-quality electron beams from a laser wakefield accelerator using plasma-channel guiding 总被引:2,自引:0,他引:2
Geddes CG Toth CS Van Tilborg J Esarey E Schroeder CB Bruhwiler D Nieter C Cary J Leemans WP 《Nature》2004,431(7008):538-541
Laser-driven accelerators, in which particles are accelerated by the electric field of a plasma wave (the wakefield) driven by an intense laser, have demonstrated accelerating electric fields of hundreds of GV m(-1) (refs 1-3). These fields are thousands of times greater than those achievable in conventional radio-frequency accelerators, spurring interest in laser accelerators as compact next-generation sources of energetic electrons and radiation. To date, however, acceleration distances have been severely limited by the lack of a controllable method for extending the propagation distance of the focused laser pulse. The ensuing short acceleration distance results in low-energy beams with 100 per cent electron energy spread, which limits potential applications. Here we demonstrate a laser accelerator that produces electron beams with an energy spread of a few per cent, low emittance and increased energy (more than 10(9) electrons above 80 MeV). Our technique involves the use of a preformed plasma density channel to guide a relativistically intense laser, resulting in a longer propagation distance. The results open the way for compact and tunable high-brightness sources of electrons and radiation. 相似文献
8.
Takamiya K Kostourou V Adams S Jadeja S Chalepakis G Scambler PJ Huganir RL Adams RH 《Nature genetics》2004,36(2):172-177
Cell adhesion to extracellular matrix (ECM) proteins is crucial for the structural integrity of tissues and epithelial-mesenchymal interactions mediating organ morphogenesis. Here we describe how the loss of a cytoplasmic multi-PDZ scaffolding protein, glutamate receptor interacting protein 1 (GRIP1), leads to the formation of subepidermal hemorrhagic blisters, renal agenesis, syndactyly or polydactyly and permanent fusion of eyelids (cryptophthalmos). Similar malformations are characteristic of individuals with Fraser syndrome and animal models of this human genetic disorder, such as mice carrying the blebbed mutation (bl) in the gene encoding the Fras1 ECM protein. GRIP1 can physically interact with Fras1 and is required for the localization of Fras1 to the basal side of cells. In one animal model of Fraser syndrome, the eye-blebs (eb) mouse, Grip1 is disrupted by a deletion of two coding exons. Our data indicate that GRIP1 is required for normal cell-matrix interactions during early embryonic development and that inactivation of Grip1 causes Fraser syndrome-like defects in mice. 相似文献
9.
An Hfe-dependent pathway mediates hyposideremia in response to lipopolysaccharide-induced inflammation in mice 总被引:19,自引:0,他引:19
Roy CN Custodio AO de Graaf J Schneider S Akpan I Montross LK Sanchez M Gaudino A Hentze MW Andrews NC Muckenthaler MU 《Nature genetics》2004,36(5):481-485
Inflammation influences iron balance in the whole organism. A common clinical manifestation of these changes is anemia of chronic disease (ACD; also called anemia of inflammation). Inflammation reduces duodenal iron absorption and increases macrophage iron retention, resulting in low serum iron concentrations (hyposideremia). Despite the protection hyposideremia provides against proliferating microorganisms, this 'iron withholding' reduces the iron available to maturing red blood cells and eventually contributes to the development of anemia. Hepcidin antimicrobial peptide (Hamp) is a hepatic defensin-like peptide hormone that inhibits duodenal iron absorption and macrophage iron release. Hamp is part of the type II acute phase response and is thought to have a crucial regulatory role in sequestering iron in the context of ACD. Mice with deficiencies in the hemochromatosis gene product, Hfe, mounted a general inflammatory response after injection of lipopolysaccharide but lacked appropriate Hamp expression and did not develop hyposideremia. These data suggest a previously unidentified role for Hfe in innate immunity and ACD. 相似文献
10.
Guard cells are located in the epidermis of plant leaves, and in pairs surround stomatal pores. These control both the influx of CO2 as a raw material for photosynthesis and water loss from plants through transpiration to the atmosphere. Guard cells have become a highly developed system for dissecting early signal transduction mechanisms in plants. In response to drought, plants synthesize the hormone abscisic acid, which triggers closing of stomata, thus reducing water loss. Recently, central regulators of guard cell abscisic acid signalling have been discovered. The molecular understanding of the guard cell signal transduction network opens possibilities for engineering stomatal responses to control CO2 intake and plant water loss. 相似文献