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951.
Pani A Batetta B Putzolu M Sanna F Spano O Piras S Mulas MF Bonatesta RR Amat di S Filippo C Vargiu L Marceddu T Sanna L La Colla P Dessì S 《Cellular and molecular life sciences : CMLS》2000,57(7):1094-1102
The product of the MDR1 gene (P-gp) has been implicated in the transport of cholesterol from plasma membrane to endoplasmic reticulum for esterification.
In previous studies on leukemia cell lines, we suggested that cholesterol esterification may regulate the rate of cell growth
and that the MDR1 gene might be involved in this process by modulating intracellular cholesterol esters levels. To further investigate this
matter, the rate of cell growth, cholesterol metabolism, expression of the MDR1 gene, and P-gp activity were compared in KB cell lines displaying differences in expression and function of P-gp (drug-sensitive
phenotype versus MDR phenotype). The rate of cell growth correlated with cholesterol esterification in all KB cell lines,
whereas the over-expression of MDR1 observed in the MDR cell lines was not always associated with an increased capacity of cells to esterify cholesterol. Two
known inhibitors of P-gp activity, progesterone and verapamil, strongly inhibited both cholesterol esterification and cell
proliferation in all KB cell lines, but they affected intracellular accumulation of labeled vinblastine only in MDR cell lines.
These results further support a role for cholesterol esters in the regulation of cell growth and suggest that the P-gp expressed
in MDR KB cells is not involved in the general process leading to cholesterol esterification.
Received 14 February 2000; received after revision 10 April 2000; accepted 8 May 2000 相似文献
952.
Immunoglobulin light chains are the precursor proteins for fibrils that are formed during primary amyloidosis and in amyloidosis associated with multiple myeloma. As found for the approximately 20 currently described forms of focal, localized, or systemic amyloidoses, light chain-related fibrils extracted from physiological deposits are invariably associated with glycosaminoglycans, predominantly heparan sulfate. Other amyloid-related proteins are either structurally normal, such as beta2-microglobulin and islet amyloid polypeptide, fragments of normal proteins such as serum amyloid A protein or the precursor protein of the beta peptide involved in Alzheimer's disease, or are inherited forms of single amino acid variants of a normal protein such as found in the familial forms of amyloid associated with transthyretin. In contrast, the primary structures of light chains involved in fibril formation exhibit extensive mutational diversity rendering some proteins highly amyloidogenic and others non-pathological. The interactions between light chains and glycosaminoglycans are also affected by amino acid variation and may influence the clinical course of disease by enhancing fibril stability and contributing to resistance to protease degradation. Relatively little is currently known about the mechanisms by which glycosaminoglycans interact with light chains and light-chain fibrils. It is probable that future studies of this uniquely diverse family of proteins will continue to shed light on the processes of amyloidosis, and contribute as well to a greater understanding of the normal physiological roles of glycosaminoglycans. 相似文献
953.
Calvete JJ Costa FH Saker-Sampaio S Murciano MP Nagano CS Cavada BS Grangeiro TB Ramos MV Bloch C Silveira SB Freitas BT Sampaio AH 《Cellular and molecular life sciences : CMLS》2000,57(2):343-350
The primary structure of a lectin isolated from the red alga Bryothamnion triquetrum was established by combination of Edman degradation of sets of overlapping peptides and mass spectrometry. It contains 91 amino acids and two disulphide bonds. The primary structure of the B. triquetrum lectin does not show amino acid sequence similarity with known plant and animal lectin structures. Hence, this protein may be the paradigm of a novel lectin family. 相似文献
954.
Differential basal synthesis of Hsp70/Hsc70 contributes to interindividual variation in Hsp70/Hsc70 inducibility 总被引:7,自引:0,他引:7
Boshoff T Lombard F Eiselen R Bornman JJ Bachelet M Polla BS Bornman L 《Cellular and molecular life sciences : CMLS》2000,57(8-9):1317-1325
The source of intraspecies variation in the expression of heat shock proteins (HSPs) remains unresolved but could shed light
on differential stress tolerance and disease susceptibility. This study investigated the influence of variable basal HSP synthesis
on differential inducibility of HSP synthesis. Basal and heat-induced synthesis of the major HSP families in peripheral blood
monocytes from healthy donors (n=42) were analysed using biometabolic labelling and densitometry. Basal Hsp70/Hsc70 synthesis
and percentage induction of Hsp70/Hsc70 synthesis were significantly correlated (r=−0.57, p<0.0001), and described most accurately
by an exponential decay equation (R=0.68, R2=0.46). This regression equation suggests that increasing levels of basal Hsp70/Hsc70 synthesis are accompanied byan exponential
decrease in the percentage induction of Hsp70/Hsc70 synthesis. The model fits data from European and non-European population
groups independently, although both coefficients in the regression equation were larger for non-Europeans. This implies population
group as an additional factor influencing differential HSP expression. The differential inducibility of Hsp70/Hsc70 due to
variable basal synthesis of Hsp70/Hsc70 and based upon population group may contribute to differential stress tolerance or
disease susceptibility.
Received 27 March 2000; received after revision 19 June 2000; accepted 20 June 2000 相似文献
955.
Roest Crollius H Jaillon O Bernot A Dasilva C Bouneau L Fischer C Fizames C Wincker P Brottier P Quétier F Saurin W Weissenbach J 《Nature genetics》2000,25(2):235-238
The number of genes in the human genome is unknown, with estimates ranging from 50,000 to 90,000 (refs 1, 2), and to more than 140,000 according to unpublished sources. We have developed 'Exofish', a procedure based on homology searches, to identify human genes quickly and reliably. This method relies on the sequence of another vertebrate, the pufferfish Tetraodon nigroviridis, to detect conserved sequences with a very low background. Similar to Fugu rubripes, a marine pufferfish proposed by Brenner et al. as a model for genomic studies, T. nigroviridis is a more practical alternative with a genome also eight times more compact than that of human. Many comparisons have been made between F. rubripes and human DNA that demonstrate the potential of comparative genomics using the pufferfish genome. Application of Exofish to the December version of the working draft sequence of the human genome and to Unigene showed that the human genome contains 28,000-34,000 genes, and that Unigene contains less than 40% of the protein-coding fraction of the human genome. 相似文献
956.
957.
958.
Hypoglycaemia, liver necrosis and perinatal death in mice lacking all isoforms of phosphoinositide 3-kinase p85 alpha 总被引:11,自引:0,他引:11
Fruman DA Mauvais-Jarvis F Pollard DA Yballe CM Brazil D Bronson RT Kahn CR Cantley LC 《Nature genetics》2000,26(3):379-382
Phosphoinositide 3-kinases produce 3'-phosphorylated phosphoinositides that act as second messengers to recruit other signalling proteins to the membrane. Pi3ks are activated by many extracellular stimuli and have been implicated in a variety of cellular responses. The Pi3k gene family is complex and the physiological roles of different classes and isoforms are not clear. The gene Pik3r1 encodes three proteins (p85 alpha, p55 alpha and p50 alpha) that serve as regulatory subunits of class IA Pi3ks (ref. 2). Mice lacking only the p85 alpha isoform are viable but display hypoglycaemia and increased insulin sensitivity correlating with upregulation of the p55 alpha and p50 alpha variants. Here we report that loss of all protein products of Pik3r1 results in perinatal lethality. We observed, among other abnormalities, extensive hepatocyte necrosis and chylous ascites. We also noted enlarged skeletal muscle fibres, brown fat necrosis and calcification of cardiac tissue. In liver and muscle, loss of the major regulatory isoform caused a great decrease in expression and activity of class IA Pi3k catalytic subunits; nevertheless, homozygous mice still displayed hypoglycaemia, lower insulin levels and increased glucose tolerance. Our findings reveal that p55 alpha and/or p50 alpha are required for survival, but not for development of hypoglycaemia, in mice lacking p85 alpha. 相似文献
959.
Atmospheric methyl bromide (CH3Br) and methyl chloride (CH3Cl), compounds that are involved in stratospheric ozone depletion, originate from both natural and anthropogenic sources. Current estimates of CH3Br and CH3Cl emissions from oceanic sources, terrestrial plants and fungi, biomass burning and anthropogenic inputs do not balance their losses owing to oxidation by hydroxyl radicals, oceanic degradation, and consumption in soils, suggesting that additional natural terrestrial sources may be important. Here we show that CH3Br and CH3Cl are released to the atmosphere from all vegetation zones of two coastal salt marshes. We see very large fluxes of CH3Br and CH3Cl per unit area: up to 42 and 570 micromol m(-2) d(-1), respectively. The fluxes show large diurnal, seasonal and spatial variabilities, but there is a strong correlation between the fluxes of CH3Br and those of CH3Cl, with an average molar flux ratio of roughly 1:20. If our measurements are typical of salt marshes globally, they suggest that such ecosystems, even though they constitute less than 0.1% of the global surface area, may produce roughly 10% of the total fluxes of atmospheric CH3Br and CH3Cl. 相似文献
960.