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951.
The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design 总被引:1,自引:0,他引:1
Russell RJ Haire LF Stevens DJ Collins PJ Lin YP Blackburn GM Hay AJ Gamblin SJ Skehel JJ 《Nature》2006,443(7107):45-49
The worldwide spread of H5N1 avian influenza has raised concerns that this virus might acquire the ability to pass readily among humans and cause a pandemic. Two anti-influenza drugs currently being used to treat infected patients are oseltamivir (Tamiflu) and zanamivir (Relenza), both of which target the neuraminidase enzyme of the virus. Reports of the emergence of drug resistance make the development of new anti-influenza molecules a priority. Neuraminidases from influenza type A viruses form two genetically distinct groups: group-1 contains the N1 neuraminidase of the H5N1 avian virus and group-2 contains the N2 and N9 enzymes used for the structure-based design of current drugs. Here we show by X-ray crystallography that these two groups are structurally distinct. Group-1 neuraminidases contain a cavity adjacent to their active sites that closes on ligand binding. Our analysis suggests that it may be possible to exploit the size and location of the group-1 cavity to develop new anti-influenza drugs. 相似文献
952.
Fox DW Yost S Kulkarni SR Torii K Kato T Yamaoka H Sako M Harrison FA Sari R Price PA Berger E Soderberg AM Djorgovski SG Barth AJ Pravdo SH Frail DA Gal-Yam A Lipkin Y Mauch T Harrison C Buttery H 《Nature》2003,422(6929):284-286
Observations of the long-lived emission--or 'afterglow'--of long-duration gamma-ray bursts place them at cosmological distances, but the origin of these energetic explosions remains a mystery. Observations of optical emission contemporaneous with the burst of gamma-rays should provide insight into the details of the explosion, as well as into the structure of the surrounding environment. One bright optical flash was detected during a burst, but other efforts have produced negative results. Here we report the discovery of the optical counterpart of GRB021004 only 193 seconds after the event. The initial decline is unexpectedly slow and requires varying energy content in the gamma-ray burst blastwave over the course of the first hour. Further analysis of the X-ray and optical afterglow suggests additional energy variations over the first few days. 相似文献
953.
MHC polymorphism pre-dating speciation 总被引:24,自引:0,他引:24
Two features distinguish the polymorphism of the major histocompatibility complex (MHC) loci from that of other loci: its high diversity and the large genetic distance between MHC alleles. More than 100 alleles exist in natural populations in the mouse at each of the functional class I and class II alleles, all alleles occurring at frequencies that cannot be explained by recurrent mutations. Some of the alleles differ by approximately 70 nucleotides in the coding region alone and some of the products of the allelic genes differ by more than 50 amino acids. It has generally been assumed that these differences accumulated after species inception. Here, we present evidence for an alternative explanation of the origin of MHC polymorphism: a large part of the MHC polymorphism pre-dates speciation and is passed on from species to species. We describe allelic differences that must have arisen before the separation of mice and rats from a common ancestor more than 10 million years ago. 相似文献
954.
Iverson RM Dzurisin D Gardner CA Gerlach TM LaHusen RG Lisowski M Major JJ Malone SD Messerich JA Moran SC Pallister JS Qamar AI Schilling SP Vallance JW 《Nature》2006,444(7118):439-443
The 2004-05 eruption of Mount St Helens exhibited sustained, near-equilibrium behaviour characterized by relatively steady extrusion of a solid dacite plug and nearly periodic shallow earthquakes. Here we present a diverse data set to support our hypothesis that these earthquakes resulted from stick-slip motion along the margins of the plug as it was forced incrementally upwards by ascending, solidifying, gas-poor magma. We formalize this hypothesis with a dynamical model that reveals a strong analogy between behaviour of the magma-plug system and that of a variably damped oscillator. Modelled stick-slip oscillations have properties that help constrain the balance of forces governing the earthquakes and eruption, and they imply that magma pressure never deviated much from the steady equilibrium pressure. We infer that the volcano was probably poised in a near-eruptive equilibrium state long before the onset of the 2004-05 eruption. 相似文献
955.
Summary Thymidylate synthetase (methylenetetrahydrofolate: 2-deoxyuridine-5-monophosphate C-methyltransferase; EC 2.1.1.45) from neonatal mouse liver has been purified 714-fold by affinity chromatography on aminohexylsepharose bound 10-methyl-5,8-dideazafolate.Supported by grant CA22754, awarded by the National Cancer Institute, DHEW. 相似文献
956.
van de Laar IM Oldenburg RA Pals G Roos-Hesselink JW de Graaf BM Verhagen JM Hoedemaekers YM Willemsen R Severijnen LA Venselaar H Vriend G Pattynama PM Collée M Majoor-Krakauer D Poldermans D Frohn-Mulder IM Micha D Timmermans J Hilhorst-Hofstee Y Bierma-Zeinstra SM Willems PJ Kros JM Oei EH Oostra BA Wessels MW Bertoli-Avella AM 《Nature genetics》2011,43(2):121-126
Thoracic aortic aneurysms and dissections are a main feature of connective tissue disorders, such as Marfan syndrome and Loeys-Dietz syndrome. We delineated a new syndrome presenting with aneurysms, dissections and tortuosity throughout the arterial tree in association with mild craniofacial features and skeletal and cutaneous anomalies. In contrast with other aneurysm syndromes, most of these affected individuals presented with early-onset osteoarthritis. We mapped the genetic locus to chromosome 15q22.2-24.2 and show that the disease is caused by mutations in SMAD3. This gene encodes a member of the TGF-β pathway that is essential for TGF-β signal transmission. SMAD3 mutations lead to increased aortic expression of several key players in the TGF-β pathway, including SMAD3. Molecular diagnosis will allow early and reliable identification of cases and relatives at risk for major cardiovascular complications. Our findings endorse the TGF-β pathway as the primary pharmacological target for the development of new treatments for aortic aneurysms and osteoarthritis. 相似文献
957.
Frustrated systems are ubiquitous, and they are interesting because their behaviour is difficult to predict; frustration can lead to macroscopic degeneracies and qualitatively new states of matter. Magnetic systems offer good examples in the form of spin lattices, where all interactions between spins cannot be simultaneously satisfied. Here we report how unusual composite spin degrees of freedom can emerge from frustrated magnetic interactions in the cubic spinel ZnCr(2)O(4). Upon cooling, groups of six spins self-organize into weakly interacting antiferromagnetic loops, whose directors -- the unique direction along which the spins are aligned, parallel or antiparallel -- govern all low-temperature dynamics. The experimental evidence comes from a measurement of the magnetic form factor by inelastic neutron scattering; the data show that neutrons scatter from hexagonal spin clusters rather than individual spins. The hexagon directors are, to a first approximation, decoupled from each other, and hence their reorientations embody the long-sought local zero energy modes for the pyrochlore lattice. 相似文献
958.
959.
960.
In 1997-98, fires associated with an exceptional drought caused by the El Ni?o/Southern Oscillation (ENSO) devastated large areas of tropical rain forests worldwide. Evidence suggests that in tropical rainforest environments selective logging may lead to an increased susceptibility of forests to fire. We investigated whether this was true in the Indonesian fires, the largest fire disaster ever observed. We performed a multiscale analysis using coarse- and high-resolution optical and radar satellite imagery assisted by ground and aerial surveys to assess the extent of the fire-damaged area and the effect on vegetation in East Kalimantan on the island of Borneo. A total of 5.2 +/- 0.3 million hectares including 2.6 million hectares of forest was burned with varying degrees of damage. Forest fires primarily affected recently logged forests; primary forests or those logged long ago were less affected. These results support the hypothesis of positive feedback between logging and fire occurrence. The fires severely damaged the remaining forests and significantly increased the risk of recurrent fire disasters by leaving huge amounts of dead flammable wood. 相似文献