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811.
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
812.
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
813.
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
814.
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
815.
Thye T Owusu-Dabo E Vannberg FO van Crevel R Curtis J Sahiratmadja E Balabanova Y Ehmen C Muntau B Ruge G Sievertsen J Gyapong J Nikolayevskyy V Hill PC Sirugo G Drobniewski F van de Vosse E Newport M Alisjahbana B Nejentsev S Ottenhoff TH Hill AV Horstmann RD Meyer CG 《Nature genetics》2012,44(3):257-259
After imputation of data from the 1000 Genomes Project into a genome-wide dataset of Ghanaian individuals with tuberculosis and controls, we identified a resistance locus on chromosome 11p13 downstream of the WT1 gene (encoding Wilms tumor 1). The strongest signal was obtained at the rs2057178 SNP (P = 2.63 × 10(-9)). Replication in Gambian, Indonesian and Russian tuberculosis case-control study cohorts increased the significance level for the association with this SNP to P = 2.57 × 10(-11). 相似文献
816.
Somnath Mukhopadhyay Adriano O. Solis Rafael S. Gutierrez 《Journal of forecasting》2012,31(8):721-735
Forecasting for inventory items with lumpy demand is difficult because of infrequent nonzero demands with high variability. This article developed two methods to forecast lumpy demand: an optimally weighted moving average method and an intelligent pattern‐seeking method. We compare them with a number of well‐referenced methods typically applied over the last 30 years in forecasting intermittent or lumpy demand. The comparison is conducted over about 200,000 forecasts (using 1‐day‐ahead and 5‐day‐ahead review periods) for 24 series of actual product demands across four different error measures. One of the most important findings of our study is that the two non‐traditional methods perform better overall than the traditional methods. We summarize results and discuss managerial implications. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献
817.
Glejzer A Laudet E Leprince P Hennuy B Poulet C Shakhova O Sommer L Rogister B Wislet-Gendebien S 《Cellular and molecular life sciences : CMLS》2011,68(12):2101-2114
Recent studies have shown that neural crest-derived progenitor cells can be found in diverse mammalian tissues including tissues
that were not previously shown to contain neural crest derivatives, such as bone marrow. The identification of those "new" neural
crest-derived progenitor cells opens new strategies for developing autologous cell replacement therapies in regenerative medicine.
However, their potential use is still a challenge as only few neural crest-derived progenitor cells were found in those new
accessible locations. In this study, we developed a protocol, based on wnt1 and BMP2 effects, to enrich neural crest-derived
cells from adult bone marrow. Those two factors are known to maintain and stimulate the proliferation of embryonic neural
crest stem cells, however, their effects have never been characterized on neural crest cells isolated from adult tissues.
Using multiple strategies from microarray to 2D-DIGE proteomic analyses, we characterized those recruited neural crest-derived
cells, defining their identity and their differentiating abilities. 相似文献
818.
Holm H Gudbjartsson DF Sulem P Masson G Helgadottir HT Zanon C Magnusson OT Helgason A Saemundsdottir J Gylfason A Stefansdottir H Gretarsdottir S Matthiasson SE Thorgeirsson GM Jonasdottir A Sigurdsson A Stefansson H Werge T Rafnar T Kiemeney LA Parvez B Muhammad R Roden DM Darbar D Thorleifsson G Walters GB Kong A Thorsteinsdottir U Arnar DO Stefansson K 《Nature genetics》2011,43(4):316-320
Through complementary application of SNP genotyping, whole-genome sequencing and imputation in 38,384 Icelanders, we have discovered a previously unidentified sick sinus syndrome susceptibility gene, MYH6, encoding the alpha heavy chain subunit of cardiac myosin. A missense variant in this gene, c.2161C>T, results in the conceptual amino acid substitution p.Arg721Trp, has an allelic frequency of 0.38% in Icelanders and associates with sick sinus syndrome with an odds ratio = 12.53 and P = 1.5 × 10?2?. We show that the lifetime risk of being diagnosed with sick sinus syndrome is around 6% for non-carriers of c.2161C>T but is approximately 50% for carriers of the c.2161C>T variant. 相似文献
819.
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
820.
Polycystic kidney diseases (PKDs) represent a large group of progressive renal disorders characterized by the development
of renal cysts leading to end-stage renal disease. Enormous strides have been made in understanding the pathogenesis of PKDs
and the development of new therapies. Studies of autosomal dominant and recessive polycystic kidney diseases converge on molecular
mechanisms of cystogenesis, including ciliary abnormalities and intracellular calcium dysregulation, ultimately leading to
increased proliferation, apoptosis and dedifferentiation. Here we review the pathobiology of PKD, highlighting recent progress
in elucidating common molecular pathways of cystogenesis. We discuss available models and challenges for therapeutic discovery
as well as summarize the results from preclinical experimental treatments targeting key disease-specific pathways.
Received 8 August 2007; received after revision 19 September 2007; accepted 2 October 2007 相似文献