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971.
The anterior/posterior (A/P) and dorsal/ventral (D/V) compartment borders that subdivide the wing imaginal discs of Drosophila third instar larvae are each associated with a developmental organizer. Decapentaplegic (Dpp), a member of the transforming growth factor-beta (TGF-beta) superfamily, embodies the activity of the A/P organizer. It is produced at the A/P organizer and distributes in a gradient of decreasing concentration to regulate target genes, functioning non-autonomously to regulate growth and patterning of both the anterior and posterior compartments. Wingless (Wg) is produced at the D/V organizer and embodies its activity. The mechanisms that distribute Dpp and Wg are not known, but proposed mechanisms include extracellular diffusion, successive transfers between neighbouring cells, vesicle-mediated movement, and direct transfer via cytonemes. Cytonemes are actin-based filopodial extensions that have been found to orient towards the A/P organizer from outlying cells. Here we show that in the wing disc, cytonemes orient towards both the A/P and D/V organizers, and that their presence and orientation correlates with Dpp signalling. We also show that the Dpp receptor, Thickveins (Tkv), is present in punctae that move along cytonemes. These observations are consistent with a role for cytonemes in signal transduction. 相似文献
972.
Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways 总被引:21,自引:0,他引:21
Simons M Gloy J Ganner A Bullerkotte A Bashkurov M Krönig C Schermer B Benzing T Cabello OA Jenny A Mlodzik M Polok B Driever W Obara T Walz G 《Nature genetics》2005,37(5):537-543
Cystic renal diseases are caused by mutations of proteins that share a unique subcellular localization: the primary cilium of tubular epithelial cells. Mutations of the ciliary protein inversin cause nephronophthisis type II, an autosomal recessive cystic kidney disease characterized by extensive renal cysts, situs inversus and renal failure. Here we report that inversin acts as a molecular switch between different Wnt signaling cascades. Inversin inhibits the canonical Wnt pathway by targeting cytoplasmic dishevelled (Dsh or Dvl1) for degradation; concomitantly, it is required for convergent extension movements in gastrulating Xenopus laevis embryos and elongation of animal cap explants, both regulated by noncanonical Wnt signaling. In zebrafish, the structurally related switch molecule diversin ameliorates renal cysts caused by the depletion of inversin, implying that an inhibition of canonical Wnt signaling is required for normal renal development. Fluid flow increases inversin levels in ciliated tubular epithelial cells and seems to regulate this crucial switch between Wnt signaling pathways during renal development. 相似文献
973.
974.
Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer 总被引:25,自引:0,他引:25
Fraga MF Ballestar E Villar-Garea A Boix-Chornet M Espada J Schotta G Bonaldi T Haydon C Ropero S Petrie K Iyer NG Pérez-Rosado A Calvo E Lopez JA Cano A Calasanz MJ Colomer D Piris MA Ahn N Imhof A Caldas C Jenuwein T Esteller M 《Nature genetics》2005,37(4):391-400
CpG island hypermethylation and global genomic hypomethylation are common epigenetic features of cancer cells. Less attention has been focused on histone modifications in cancer cells. We characterized post-translational modifications to histone H4 in a comprehensive panel of normal tissues, cancer cell lines and primary tumors. Using immunodetection, high-performance capillary electrophoresis and mass spectrometry, we found that cancer cells had a loss of monoacetylated and trimethylated forms of histone H4. These changes appeared early and accumulated during the tumorigenic process, as we showed in a mouse model of multistage skin carcinogenesis. The losses occurred predominantly at the acetylated Lys16 and trimethylated Lys20 residues of histone H4 and were associated with the hypomethylation of DNA repetitive sequences, a well-known characteristic of cancer cells. Our data suggest that the global loss of monoacetylation and trimethylation of histone H4 is a common hallmark of human tumor cells. 相似文献
975.
Mutations in SEPT9 cause hereditary neuralgic amyotrophy 总被引:7,自引:0,他引:7
Kuhlenbäumer G Hannibal MC Nelis E Schirmacher A Verpoorten N Meuleman J Watts GD De Vriendt E Young P Stögbauer F Halfter H Irobi J Goossens D Del-Favero J Betz BG Hor H Kurlemann G Bird TD Airaksinen E Mononen T Serradell AP Prats JM Van Broeckhoven C De Jonghe P Timmerman V Ringelstein EB Chance PF 《Nature genetics》2005,37(10):1044-1046
Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant recurrent neuropathy affecting the brachial plexus. HNA is triggered by environmental factors such as infection or parturition. We report three mutations in the gene septin 9 (SEPT9) in six families with HNA linked to chromosome 17q25. HNA is the first monogenetic disease caused by mutations in a gene of the septin family. Septins are implicated in formation of the cytoskeleton, cell division and tumorigenesis. 相似文献
976.
Vogt G Chapgier A Yang K Chuzhanova N Feinberg J Fieschi C Boisson-Dupuis S Alcais A Filipe-Santos O Bustamante J de Beaucoudrey L Al-Mohsen I Al-Hajjar S Al-Ghonaium A Adimi P Mirsaeidi M Khalilzadeh S Rosenzweig S de la Calle Martin O Bauer TR Puck JM Ochs HD Furthner D Engelhorn C Belohradsky B Mansouri D Holland SM Schreiber RD Abel L Cooper DN Soudais C Casanova JL 《Nature genetics》2005,37(7):692-700
Mutations involving gains of glycosylation have been considered rare, and the pathogenic role of the new carbohydrate chains has never been formally established. We identified three children with mendelian susceptibility to mycobacterial disease who were homozygous with respect to a missense mutation in IFNGR2 creating a new N-glycosylation site in the IFNgammaR2 chain. The resulting additional carbohydrate moiety was both necessary and sufficient to abolish the cellular response to IFNgamma. We then searched the Human Gene Mutation Database for potential gain-of-N-glycosylation missense mutations; of 10,047 mutations in 577 genes encoding proteins trafficked through the secretory pathway, we identified 142 candidate mutations ( approximately 1.4%) in 77 genes ( approximately 13.3%). Six mutant proteins bore new N-linked carbohydrate moieties. Thus, an unexpectedly high proportion of mutations that cause human genetic disease might lead to the creation of new N-glycosylation sites. Their pathogenic effects may be a direct consequence of the addition of N-linked carbohydrate. 相似文献
977.
Remobilization of southern African desert dune systems by twenty-first century global warming 总被引:3,自引:0,他引:3
Although desert dunes cover 5 per cent of the global land surface and 30 per cent of Africa, the potential impacts of twenty-first century global warming on desert dune systems are not well understood. The inactive Sahel and southern African dune systems, which developed in multiple arid phases since the last interglacial period, are used today by pastoral and agricultural systems that could be disrupted if climate change alters twenty-first century dune dynamics. Empirical data and model simulations have established that the interplay between dune surface erodibility (determined by vegetation cover and moisture availability) and atmospheric erosivity (determined by wind energy) is critical for dunefield dynamics. This relationship between erodibility and erosivity is susceptible to climate-change impacts. Here we use simulations with three global climate models and a range of emission scenarios to assess the potential future activity of three Kalahari dunefields. We determine monthly values of dune activity by modifying and improving an established dune mobility index so that it can account for global climate model data outputs. We find that, regardless of the emission scenario used, significantly enhanced dune activity is simulated in the southern dunefield by 2039, and in the eastern and northern dunefields by 2069. By 2099 all dunefields are highly dynamic, from northern South Africa to Angola and Zambia. Our results suggest that dunefields are likely to be reactivated (the sand will become significantly exposed and move) as a consequence of twenty-first century climate warming. 相似文献
978.
979.
Tomasko MG Archinal B Becker T Bézard B Bushroe M Combes M Cook D Coustenis A de Bergh C Dafoe LE Doose L Douté S Eibl A Engel S Gliem F Grieger B Holso K Howington-Kraus E Karkoschka E Keller HU Kirk R Kramm R Küppers M Lanagan P Lellouch E Lemmon M Lunine J McFarlane E Moores J Prout GM Rizk B Rosiek M Rueffer P Schröder SE Schmitt B See C Smith P Soderblom L Thomas N West R 《Nature》2005,438(7069):765-778
The irreversible conversion of methane into higher hydrocarbons in Titan's stratosphere implies a surface or subsurface methane reservoir. Recent measurements from the cameras aboard the Cassini orbiter fail to see a global reservoir, but the methane and smog in Titan's atmosphere impedes the search for hydrocarbons on the surface. Here we report spectra and high-resolution images obtained by the Huygens Probe Descent Imager/Spectral Radiometer instrument in Titan's atmosphere. Although these images do not show liquid hydrocarbon pools on the surface, they do reveal the traces of once flowing liquid. Surprisingly like Earth, the brighter highland regions show complex systems draining into flat, dark lowlands. Images taken after landing are of a dry riverbed. The infrared reflectance spectrum measured for the surface is unlike any other in the Solar System; there is a red slope in the optical range that is consistent with an organic material such as tholins, and absorption from water ice is seen. However, a blue slope in the near-infrared suggests another, unknown constituent. The number density of haze particles increases by a factor of just a few from an altitude of 150 km to the surface, with no clear space below the tropopause. The methane relative humidity near the surface is 50 per cent. 相似文献
980.
Lister AM Edwards CJ Nock DA Bunce M van Pijlen IA Bradley DG Thomas MG Barnes I 《Nature》2005,438(7069):850-853
The giant deer, or 'Irish elk', has featured extensively in debates on adaptation, sexual selection, and extinction. Its huge antlers--the largest of any deer species, living or extinct--formed a focus of much past work. Yet the phylogenetic position of the giant deer has remained an enigma. On the basis of its flattened antlers, the species was previously regarded as closely related to the living fallow deer. Recent morphological studies, however, have challenged that view and placed the giant deer closer to the living red deer or wapiti. Here we present a new phylogenetic analysis encompassing morphological and DNA sequence evidence, and find that both sets of data independently support a sister-group relationship of giant and fallow deer. Our results include the successful extraction and sequencing of DNA from this extinct species, and highlight the value of a joint molecular and morphological approach. 相似文献