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641.
Involvement of chemokine receptors in breast cancer metastasis 总被引:344,自引:0,他引:344
Müller A Homey B Soto H Ge N Catron D Buchanan ME McClanahan T Murphy E Yuan W Wagner SN Barrera JL Mohar A Verástegui E Zlotnik A 《Nature》2001,410(6824):50-56
Breast cancer is characterized by a distinct metastatic pattern involving the regional lymph nodes, bone marrow, lung and liver. Tumour cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases. Their respective ligands CXCL12/SDF-1alpha and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis. In breast cancer cells, signalling through CXCR4 or CCR7 mediates actin polymerization and pseudopodia formation, and subsequently induces chemotactic and invasive responses. In vivo, neutralizing the interactions of CXCL12/CXCR4 significantly impairs metastasis of breast cancer cells to regional lymph nodes and lung. Malignant melanoma, which has a similar metastatic pattern as breast cancer but also a high incidence of skin metastases, shows high expression levels of CCR10 in addition to CXCR4 and CCR7. Our findings indicate that chemokines and their receptors have a critical role in determining the metastatic destination of tumour cells. 相似文献
642.
Twisted gastrulation can function as a BMP antagonist 总被引:5,自引:0,他引:5
Chang C Holtzman DA Chau S Chickering T Woolf EA Holmgren LM Bodorova J Gearing DP Holmes WE Brivanlou AH 《Nature》2001,410(6827):483-487
Bone morphogenetic proteins (BMPs), including the fly homologue Decapentaplegic (DPP), are important regulators of early vertebrate and invertebrate dorsal-ventral development. An evolutionarily conserved BMP regulatory mechanism operates from fly to fish, frog and mouse to control the dorsal-ventral axis determination. Several secreted factors, including the BMP antagonist chordin/Short gastrulation (SOG), modulate the activity of BMPs. In Drosophila, Twisted gastrulation (TSG) is also involved in dorsal-ventral patterning, yet the mechanism of its function is unclear. Here we report the characterization of the vertebrate Tsg homologues. We show that Tsg can block BMP function in Xenopus embryonic explants and inhibits several ventral markers in whole-frog embryos. Tsg binds directly to BMPs and forms a ternary complex with chordin and BMPs. Coexpression of Tsg with chordin leads to a more efficient inhibition of the BMP activity in ectodermal explants. Unlike other known BMP antagonists, however, Tsg also reduces several anterior markers at late developmental stages. Our data suggest that Tsg can function as a BMP inhibitor in Xenopus; furthermore, Tsg may have additional functions during frog embryogenesis. 相似文献
643.
Systems of colour vision are normally identical in all members of a species, but a single design may not be adequate for species living in a diverse range of light environments. Here we show that in the mantis shrimp Haptosquilla trispinosa, which occupies a range of depths in the ocean, long-wavelength colour receptors are individually tuned to the local light environment. The spectral sensitivity of specific classes of photoreceptor is adjusted by filters that vary between individuals. 相似文献
644.
High critical current density and enhanced irreversibility field in superconducting MgB2 thin films 总被引:5,自引:0,他引:5
Eom CB Lee MK Choi JH Belenky LJ Song X Cooley LD Naus MT Patnaik S Jiang J Rikel M Polyanskii A Gurevich A Cai XY Bu SD Babcock SE Hellstrom EE Larbalestier DC Rogado N Regan KA Hayward MA He T Slusky JS Inumaru K Haas MK Cava RJ 《Nature》2001,411(6837):558-560
The discovery of superconductivity at 39 K in magnesium diboride offers the possibility of a new class of low-cost, high-performance superconducting materials for magnets and electronic applications. This compound has twice the transition temperature of Nb3Sn and four times that of Nb-Ti alloy, and the vital prerequisite of strongly linked current flow has already been demonstrated. One possible drawback, however, is that the magnetic field at which superconductivity is destroyed is modest. Furthermore, the field which limits the range of practical applications-the irreversibility field H*(T)-is approximately 7 T at liquid helium temperature (4.2 K), significantly lower than about 10 T for Nb-Ti (ref. 6) and approximately 20 T for Nb3Sn (ref. 7). Here we show that MgB2 thin films that are alloyed with oxygen can exhibit a much steeper temperature dependence of H*(T) than is observed in bulk materials, yielding an H* value at 4.2 K greater than 14 T. In addition, very high critical current densities at 4.2 K are achieved: 1 MA cm-2 at 1 T and 105 A cm-2 at 10 T. These results demonstrate that MgB2 has potential for high-field superconducting applications. 相似文献
645.
Enhancement of the high-magnetic-field critical current density of superconducting MgB2 by proton irradiation 总被引:2,自引:0,他引:2
Bugoslavsky Y Cohen LF Perkins GK Polichetti M Tate TJ Gwilliam R Caplin AD 《Nature》2001,411(6837):561-563
Magnesium diboride, MgB2, has a relatively high superconducting transition temperature, placing it between the families of low- and high-temperature (copper oxide based) superconductors. Supercurrent flow in MgB2 is unhindered by grain boundaries, making it potentially attractive for technological applications in the temperature range 20-30 K. But in the bulk material, the critical current density (Jc) drops rapidly with increasing magnetic field strength. The magnitude and field dependence of the critical current are related to the presence of structural defects that can 'pin' the quantized magnetic vortices that permeate the material, and a lack of natural defects in MgB2 may be responsible for the rapid decline of Jc with increasing field strength. Here we show that modest levels of atomic disorder induced by proton irradiation enhance the pinning of vortices, thereby significantly increasing Jc at high field strengths. We anticipate that either chemical doping or mechanical processing should generate similar levels of disorder, and so achieve performance that is technologically attractive in an economically viable way. 相似文献
646.
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
647.
'Inverse' melting of a vortex lattice 总被引:1,自引:0,他引:1
Avraham N Khaykovich B Myasoedov Y Rappaport M Shtrikman H Feldman DE Tamegai T Kes PH Li M Konczykowski M van der Beek K Zeldov E 《Nature》2001,411(6836):451-454
Inverse melting is the process in which a crystal reversibly transforms into a liquid or amorphous phase when its temperature is decreased. Such a process is considered to be very rare, and the search for it is often hampered by the formation of non-equilibrium states or intermediate phases. Here we report the discovery of first-order inverse melting of the lattice formed by magnetic flux lines in a high-temperature superconductor. At low temperatures, disorder in the material pins the vortices, preventing the observation of their equilibrium properties and therefore the determination of whether a phase transition occurs. But by using a technique to 'dither' the vortices, we were able to equilibrate the lattice, which enabled us to obtain direct thermodynamic evidence of inverse melting of the ordered lattice into a disordered vortex phase as the temperature is decreased. The ordered lattice has larger entropy than the low-temperature disordered phase. The mechanism of the first-order phase transition changes gradually from thermally induced melting at high temperatures to a disorder-induced transition at low temperatures. 相似文献
648.
Evidence for ubiquitous strong electron-phonon coupling in high-temperature superconductors 总被引:3,自引:0,他引:3
Lanzara A Bogdanov PV Zhou XJ Kellar SA Feng DL Lu ED Yoshida T Eisaki H Fujimori A Kishio K Shimoyama JI Noda T Uchida S Hussain Z Shen ZX 《Nature》2001,412(6846):510-514
Coupling between electrons and phonons (lattice vibrations) drives the formation of the electron pairs responsible for conventional superconductivity. The lack of direct evidence for electron-phonon coupling in the electron dynamics of the high-transition-temperature superconductors has driven an intensive search for an alternative mechanism. A coupling of an electron with a phonon would result in an abrupt change of its velocity and scattering rate near the phonon energy. Here we use angle-resolved photoemission spectroscopy to probe electron dynamics-velocity and scattering rate-for three different families of copper oxide superconductors. We see in all of these materials an abrupt change of electron velocity at 50-80 meV, which we cannot explain by any known process other than to invoke coupling with the phonons associated with the movement of the oxygen atoms. This suggests that electron-phonon coupling strongly influences the electron dynamics in the high-temperature superconductors, and must therefore be included in any microscopic theory of superconductivity. 相似文献
649.
Dubois M Demé B Gulik-Krzywicki T Dedieu JC Vautrin C Désert S Perez E Zemb T 《Nature》2001,411(6838):672-675
Self-assembled structures having a regular hollow icosahedral form (such as those observed for proteins of virus capsids) can occur as a result of biomineralization processes, but are extremely rare in mineral crystallites. Compact icosahedra made from a boron oxide have been reported, but equivalent structures made of synthetic organic components such as surfactants have not hitherto been observed. It is, however, well known that lipids, as well as mixtures of anionic and cationic single chain surfactants, can readily form bilayers that can adopt a variety of distinct geometric forms: they can fold into soft vesicles or random bilayers (the so-called sponge phase) or form ordered stacks of flat or undulating membranes. Here we show that in salt-free mixtures of anionic and cationic surfactants, such bilayers can self-assemble into hollow aggregates with a regular icosahedral shape. These aggregates are stabilized by the presence of pores located at the vertices of the icosahedra. The resulting structures have a size of about one micrometre and mass of about 1010 daltons, making them larger than any known icosahedral protein assembly or virus capsid. We expect the combination of wall rigidity and holes at vertices of these icosahedral aggregates to be of practical value for controlled drug or DNA release. 相似文献
650.
Late blight, caused by the oomycete plant pathogen Phytophthora infestans, is a devastating disease of potato and was responsible for epidemics that led to the Irish potato famine in 1845 (refs 1,2,3,4,5). Before the 1980s, worldwide populations of P. infestans were dominated by a single clonal lineage, the US-1 genotype or Ib mitochondrial DNA (mtDNA) haplotype, and sexual reproduction was not documented outside Mexico, the centre of diversity of the pathogen. Here we describe the amplification and sequencing of 100-base-pair fragments of DNA from the internal transcribed spacer region 2 from 28 historic herbarium samples including Irish and British samples collected between 1845 and 1847, confirming the identity of the pathogen. We amplified a variable region of mtDNA that is present in modern Ib haplotypes of P. infestans, but absent in the other known modern haplotypes (Ia, IIa and IIb). Lesions in samples tested were not caused by the Ib haplotype of P. infestans, and so theories that assume that the Ib haplotype is the ancestral strain need to be re-evaluated. Our data emphasize the importance of using historic specimens when making inferences about historic populations. 相似文献