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781.
H.-T. Zhao S. Endo S. Ishikura R. Chung P. J. Hogg A. Hara O. El-Kabbani 《Cellular and molecular life sciences : CMLS》2009,66(9):1570-1579
l-Xylulose reductase (XR) is involved in water re-absorption and cellular osmoregulation. The crystal structure of human XR
complemented with site-directed mutagenesis (Cys138Ala) indicated that the disulfide bond in the active site between Cys138
and Cys150 is unstable and may affect the reactivity of the enzyme. The effects of reducing agents on the activities of the
wild-type and mutant enzymes indicated the reversibility of disulfide-bond formation, which resulted in three-fold decrease
in catalytic efficiency. Furthermore, the addition of cysteine (>2 mM) inactivated human XR and was accompanied by a 10-fold
decrease in catalytic efficiency. TOF-MS analysis of the inactivated enzyme showed the S-cysteinylation of Cys138 in the wild-type
and Cys150 in the mutant enzymes. Thus, the action of human XR may be regulated by cellular redox conditions through reversible
disulfide-bond formation and by S-cysteinylation.
Received 25 January 2009; received after revision 12 February 2009; accepted 16 February 2009
H.-T. Zhao, S. Endo: These two authors contribute equally to this work. 相似文献
782.
Tenesa A Farrington SM Prendergast JG Porteous ME Walker M Haq N Barnetson RA Theodoratou E Cetnarskyj R Cartwright N Semple C Clark AJ Reid FJ Smith LA Kavoussanakis K Koessler T Pharoah PD Buch S Schafmayer C Tepel J Schreiber S Völzke H Schmidt CO Hampe J Chang-Claude J Hoffmeister M Brenner H Wilkening S Canzian F Capella G Moreno V Deary IJ Starr JM Tomlinson IP Kemp Z Howarth K Carvajal-Carmona L Webb E Broderick P Vijayakrishnan J Houlston RS Rennert G Ballinger D Rozek L Gruber SB 《Nature genetics》2008,40(5):631-637
In a genome-wide association study to identify loci associated with colorectal cancer (CRC) risk, we genotyped 555,510 SNPs in 1,012 early-onset Scottish CRC cases and 1,012 controls (phase 1). In phase 2, we genotyped the 15,008 highest-ranked SNPs in 2,057 Scottish cases and 2,111 controls. We then genotyped the five highest-ranked SNPs from the joint phase 1 and 2 analysis in 14,500 cases and 13,294 controls from seven populations, and identified a previously unreported association, rs3802842 on 11q23 (OR = 1.1; P = 5.8 x 10(-10)), showing population differences in risk. We also replicated and fine-mapped associations at 8q24 (rs7014346; OR = 1.19; P = 8.6 x 10(-26)) and 18q21 (rs4939827; OR = 1.2; P = 7.8 x 10(-28)). Risk was greater for rectal than for colon cancer for rs3802842 (P < 0.008) and rs4939827 (P < 0.009). Carrying all six possible risk alleles yielded OR = 2.6 (95% CI = 1.75-3.89) for CRC. These findings extend our understanding of the role of common genetic variation in CRC etiology. 相似文献
783.
Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease 总被引:2,自引:0,他引:2
Barrett JC Hansoul S Nicolae DL Cho JH Duerr RH Rioux JD Brant SR Silverberg MS Taylor KD Barmada MM Bitton A Dassopoulos T Datta LW Green T Griffiths AM Kistner EO Murtha MT Regueiro MD Rotter JI Schumm LP Steinhart AH Targan SR Xavier RJ;NIDDK IBD Genetics Consortium Libioulle C Sandor C Lathrop M Belaiche J Dewit O Gut I Heath S Laukens D Mni M Rutgeerts P Van Gossum A Zelenika D Franchimont D Hugot JP de Vos M Vermeire S 《Nature genetics》2008,40(8):955-962
Several risk factors for Crohn's disease have been identified in recent genome-wide association studies. To advance gene discovery further, we combined data from three studies on Crohn's disease (a total of 3,230 cases and 4,829 controls) and carried out replication in 3,664 independent cases with a mixture of population-based and family-based controls. The results strongly confirm 11 previously reported loci and provide genome-wide significant evidence for 21 additional loci, including the regions containing STAT3, JAK2, ICOSLG, CDKAL1 and ITLN1. The expanded molecular understanding of the basis of this disease offers promise for informed therapeutic development. 相似文献
784.
785.
Llorca O 《Cellular and molecular life sciences : CMLS》2008,65(9):1302-1310
In mammals, the mannose receptor family consists of four members, Endo180, DEC-205, phospholipase A2 receptor and the mannose receptor. The extracellular domains of all these receptors contain a similar arrangement of domains
in which an Nterminal cysteine-rich domain is followed by a single fibronectin type II domain and eight or ten C-type lectin-like
domains. This review focuses on the threedimensional structure of the receptors in the mannose receptor family and its functional
implication. Recent research has revealed that several members of this family can exist in at least two configurations: an
extended conformation with the N-terminal cysteinerich domain pointing outwards from the cell membrane and a bent conformation
where the N-terminal domains fold back to interact with C-type lectin-like domains at the middle of the structure. Conformational
transitions between these two states seem to regulate the interaction of these receptors with ligands and their oligomerization.
Received 25 October 2007; received after revision 23 November 2007; accepted 7 December 2007 相似文献
786.
Despite the current availability of several hundreds of thousands of amino acid sequences, more than 39% of the well-defined
enzyme activities (EC numbers) are not associated with any sequence in major public databases. This wide gap separating knowledge
of biochemical function and sequence information is found in nearly all classes of enzymes. Thus, there is an urgent need
to explore the 1525 orphan enzymes (EC numbers without associated sequences), in order to progressively bridge this unwanted
gap. Improving genome annotation could unveil a significant proportion of sequenceless enzymes. Peptide mass mapping and further
genome mining would be useful to identify proper sequence for enzymes found in species for which genetic tools are missing.
Finally, the whole community must help major public databases to begin addressing the problem of missing or incomplete information.
Received 31 October 2005; received after revision 8 December 2005; accepted 20 December 2005 相似文献
787.
Laitinen OH Hytönen VP Nordlund HR Kulomaa MS 《Cellular and molecular life sciences : CMLS》2006,63(24):2992-3017
Chicken avidin and bacterial streptavidin, (strept)avidin, are proteins widely utilized in a number of applications in life
science, ranging from purification and labeling techniques to diagnostics, and from targeted drug delivery to nanotechnology.
(Strept)avidin-biotin technology relies on the extremely tight and specific affinity between (strept)avidin and biotin (dissociation
constant, Kd≈10−14–10−16 M). (Strept)avidins are also exceptionally stable proteins. To study their ligand binding and stability characteristics,
the two proteins have been extensively modified both chemically and genetically. There are excellent accounts of this technology
and chemically modified (strept)avidins, but no comprehensive reviews exist concerning genetically engineered (strept)avidins.
To fill this gap, we here go through the genetically engineered (strept)avidins, summarizing how these constructs were designed
and how they have improved our understanding of the structural and functional characteristics of these proteins, and the benefits
they have provided for (strept)avidin-biotin technology.
Received 22 June 2006; received after revision 1 August 2006; accepted 21 September 2006 相似文献
788.
Olfactory ensheathing cells have been used in several studies to promote repair in the injured spinal cord. However, cellular
interaction between olfactory ensheathing cells and glial cells induced to be reactive in the aftermath of injury site has
not been investigated. Using an in vitro model of astrogliosis, we show that reactive astrocytes expressed significantly less glial fibrillary acidic protein (GFAP)
when cultured both in direct contact with olfactory ensheathing cells and when the two cell types were separated by a porous
membrane. Immunofluorescence staining also suggested that reactive astrocytes showed decreased chondroitin sulfate proteoglycans
in the presence of olfactory ensheathing cells, although the reduction was not statistically significant. No down-regulation
of GFAP was observed when reactive astrocytes were similarly cultured with Schwann cells. Cell viability assay and bromodeoxyuridine
uptake showed that proliferation of reactive astrocytes was significantly increased in the presence of olfactory ensheathing
cells and Schwann cells.
Received 27 February 2007; received after revision 30 March 2007; accepted 3 April 2007 相似文献
789.
Le Bouffant R Cormier P Cueff A Bellé R Mulner-Lorillon O 《Cellular and molecular life sciences : CMLS》2007,64(13):1723-1734
DNA integrity checkpoint control was studied in the sea urchin early embryo. Treatment of the embryos with genotoxic agents
such as methyl methanesulfonate (MMS) or bleomycin induced the activation of a cell cycle checkpoint as evidenced by the occurrence
of a delay or an arrest in the division of the embryos and an inhibition of CDK1/cyclin B activating dephosphorylation. The
genotoxic treatment was shown to induce DNA damage that depended on the genotoxic concentration and was correlated with the
observed cell cycle delay. At low genotoxic concentrations, embryos were able to repair the DNA damage and recover from checkpoint
arrest, whereas at high doses they underwent morphological and biochemical changes characteristic of apoptosis. Finally, extracts
prepared from embryos were found to be capable of supporting DNA repair in vitro upon incubation with oligonucleotides mimicking damage. Taken together, our results demonstrate that sea urchin early embryos
contain fully functional and activatable DNA damage checkpoints. Sea urchin embryos are discussed as a promising model to
study the signaling pathways of cell cycle checkpoint, DNA repair and apoptosis, which upon deregulation play a significant
role in the origin of cancer.
Received 10 April 2007; accepted 23 April 2007 相似文献
790.
Facchin S Ruzzene M Peggion C Sartori G Carignani G Marin O Brustolon F Lopreiato R Pinna LA 《Cellular and molecular life sciences : CMLS》2007,64(19-20):2680-2689
p53-related protein kinase (PRPK), the human homologue of yeast Bud32, belonging to a small subfamily of atypical protein kinases, is inactive unless it is previously incubated with cell lysates. Here we show that such an activation of PRPK is mediated by another kinase, Akt/PKB, which phosphorylates PRPK at Ser250. We show that recombinant PRPK is phosphorylated in vitro by Akt and its phospho-form is recognized by a Ser250-phospho-specific antibody; that cell co-transfection with Akt along with wild-type PRPK, but not with its Ser250Ala mutant, results in increased PRPK phosphorylation; and that the phosphorylation of p53 at Ser15, the only known substrate of PRPK, is markedly increased by co-transfection of Akt with wild-type PRPK, but not PRPK dead mutant, and is abrogated by cell treatment with the Akt pathway inhibitor LY294002. Our data disclose an unanticipated mechanism by which PRPK can be activated and provide a functional link between this enigmatic kinase and the Akt signaling pathway. 相似文献