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991.
Yan G Zhang G Fang X Zhang Y Li C Ling F Cooper DN Li Q Li Y van Gool AJ Du H Chen J Chen R Zhang P Huang Z Thompson JR Meng Y Bai Y Wang J Zhuo M Wang T Huang Y Wei L Li J Wang Z Hu H Yang P Le L Stenson PD Li B Liu X Ball EV An N Huang Q Zhang Y Fan W Zhang X Li Y Wang W Katze MG Su B Nielsen R Yang H Wang J Wang X Wang J 《Nature biotechnology》2011,29(11):1019-1023
The nonhuman primates most commonly used in medical research are from the genus Macaca. To better understand the genetic differences between these animal models, we present high-quality draft genome sequences from two macaque species, the cynomolgus/crab-eating macaque and the Chinese rhesus macaque. Comparison with the previously sequenced Indian rhesus macaque reveals that all three macaques maintain abundant genetic heterogeneity, including millions of single-nucleotide substitutions and many insertions, deletions and gross chromosomal rearrangements. By assessing genetic regions with reduced variability, we identify genes in each macaque species that may have experienced positive selection. Genetic divergence patterns suggest that the cynomolgus macaque genome has been shaped by introgression after hybridization with the Chinese rhesus macaque. Macaque genes display a high degree of sequence similarity with human disease gene orthologs and drug targets. However, we identify several putatively dysfunctional genetic differences between the three macaque species, which may explain functional differences between them previously observed in clinical studies. 相似文献
992.
Li Y Zheng H Luo R Wu H Zhu H Li R Cao H Wu B Huang S Shao H Ma H Zhang F Feng S Zhang W Du H Tian G Li J Zhang X Li S Bolund L Kristiansen K de Smith AJ Blakemore AI Coin LJ Yang H Wang J Wang J 《Nature biotechnology》2011,29(8):723-730
Here we use whole-genome de novo assembly of second-generation sequencing reads to map structural variation (SV) in an Asian genome and an African genome. Our approach identifies small- and intermediate-size homozygous variants (1-50 kb) including insertions, deletions, inversions and their precise breakpoints, and in contrast to other methods, can resolve complex rearrangements. In total, we identified 277,243 SVs ranging in length from 1-23 kb. Validation using computational and experimental methods suggests that we achieve overall <6% false-positive rate and <10% false-negative rate in genomic regions that can be assembled, which outperforms other methods. Analysis of the SVs in the genomes of 106 individuals sequenced as part of the 1000 Genomes Project suggests that SVs account for a greater fraction of the diversity between individuals than do single-nucleotide polymorphisms (SNPs). These findings demonstrate that whole-genome de novo assembly is a feasible approach to deriving more comprehensive maps of genetic variation. 相似文献
993.
Gout patients have a high incidence of atherosclerotic coronary heart disease. Low serum paraoxonase (PON) activity is considered
a risk factor for atherosclerosis. The relationships among paraoxonase-1 (PON1) activity, oxidative stress parameters, and
atherosclerosis in gout is not known. Therefore, we determined the plasma levels of malondialdehyde (MDA), oxidized low-density
lipoprotein (Ox-LDL), and activities of PON1/superoxide dismutase (SOD) activities in 49 gout patients (mean age 44.2 ± 7.0 years)
and 42 healthy, age-matched controls (mean age 45.0 ± 9.3 years). PON1 was measured spectrophotometrically, MDA by thiobarbituric
acid method, SOD by Griess reaction, and Ox-LDL by sandwich ELISA. Lipid and other biochemical parameters were determined
by routine laboratory methods. In gout patients, PON1/SOD activities and MDA/Ox-LDL levels were 131.3 ± 25.3/75.3 ± 28.9 kU l−1 and 6.12 ± 1.67 nmol ml−1/690.1 ± 180.2 μg l−1, respectively. In controls, these were 172.5 ± 27.8/94.0 ± 26.3 kU l−1 and 4.10 ± 1.25 nmol ml−1/452.3 ± 152.1 μg l−1, respectively. Thus, in gout patients, there was a significant decrease in PON1 (P < 0.01) and SOD (P < 0.05) activities, and an increase in MDA (P < 0.01) and Ox-LDL (P < 0.01) levels compared with controls. PON1 activity correlated positively with SOD (P < 0.05), and negatively with MDA (P < 0.01) and Ox-LDL (P < 0.01). These results suggest that gout patients were in a state of oxidative stress and the protective effects of HDL against
atherosclerosis maybe dependent on PON1 activity. These findings may explain in part the reported increase in cardiovascular
mortality in gout patients. 相似文献
994.
Tetrahydrobiopterin (BH(4)) is an essential cofactor for the nitric oxide (NO) synthases and the aromatic amino acid hydroxylases. Insufficient BH(4) has been implicated in various cardiovascular and neurological disorders. GTP cyclohydrolase 1 (GTPCH-1) is the rate-limiting enzyme for de novo biosynthesis of BH(4). The authors have recently shown that the interaction of GTPCH-1 with GTP cyclohydrolase feedback regulatory protein (GFRP) inhibits endothelial GTPCH-1 enzyme activity, BH(4) levels, and NO production. They propose that agents that disrupt the GTPCH-1/GFRP interaction can increase cellular GTPCH-1 activity, BH(4) levels, and NO production. They developed and optimized a novel time-resolved fluorescence resonance energy transfer (TR-FRET) assay to monitor the interaction of GTPCH-1 and GFRP. This assay is highly sensitive and stable and has a signal-to-background ratio (S/B) greater than 12 and a Z' factor greater than 0.8. This assay was used in an ultra-high-throughput screening (uHTS) format to screen the Library of Pharmacologically Active Compounds. Using independent protein-protein interaction and cellular activity assays, the authors identified compounds that disrupt GTPCH-1/GFRP binding and increase endothelial cell biopterin levels. Thus, this TR-FRET assay could be applied in future uHTS of additional libraries to search for molecules that increase GTPCH-1 activity and BH(4) levels. 相似文献
995.
Vujčić M Lazić M Milenković M Sladić D Radulović S Filipović N Anđelković K 《Journal of biochemical and molecular toxicology》2011,25(3):175-182
Organometallic Cd(II) compounds have recently attracted attention for their anticancer activity. The interaction of the dinuclear complex of Cd(II) with the condensation product of 2-acetylpyridine and malonic acid dihydrazide, N',N'(2) -bis[(1E)-1-(2-pyridyl)ethylidene]propanedihydrazide (Cd(II)H(2) L), with calf thymus DNA (CT-DNA) was monitored by blue shift in UV-vis spectra of the complex. The binding constant of Cd(II)H(2) L complex with CT-DNA was determined (K(B) = 1.8 × 10(4) M(-1) ) and was indicative of minor groove binding. Agarose gel electrophoretic changes in mobility of supercoiled and circular forms of pBR322 and pUC18 plasmids in the presence of the complex suggest that conformational changes in the plasmids occur upon binding of the Cd(II)H(2) L complex. The Cd(II)H(2) L complex induced perturbation of the cell cycle phase distribution and an increase in the percentage of cells in the sub-G1 phase of human cervical cancer HeLa cell line and murine melanoma B16 cell line. Immunoblotting analysis showed the overexpression of Bcl-2 protein with the Cd(II)H(2) L complex. 相似文献
996.
We examined group B streptococcus (GBS) isolates colonizing women at the 35-37 weeks of pregnancy. A total of 257 group B streptococcus (GBS) isolates for serotyped using direct agglutination with a set of commercially available antisera (Ia, Ib, II, III, IV, and V) and tested for susceptibility to antimicrobials (penicillin, macrolides, lincosamides, fluoroquinolones and tetracyclines). Fourteen isolates could not be serotyped with the antisera set used in the study. Serotype III was the predominant serotype (33%), followed by serotypes V (23%), and Ia (20%). Whereas all isolates were susceptible to penicillin, the rates of susceptibility to the other antimicrobials tested were the following: 91% for ofloxacin, 80% for clindamycin, 77% for erythromycin, and 4% for tetracycline. More than half (67%) of the macrolide resistant isolates belonged to serotypes V and III. A systematic surveillance of the autochthonous GBS serotypes, performed at the level of laboratories processing a high number of human specimens, is mandatory for strengthening the national epidemiological GBS surveillance. While penicillin remains the drug of choice for intrapartum prophylaxis, the resistance of autochthonous GBS isolates to other antibiotics should be actively monitored. 相似文献
997.
Zichen?Zhang Jianghua?Li Long?LiuEmail author Jun?Sun Zhaozhe?Hua Guocheng?Du Jian?Chen 《Biotechnology and Bioprocess Engineering》2011,16(1):107-113
The study aimed to produce 2-O-α-D-glucopyranosyl-L-ascorbic acid (AA-2G) via the transglycosylation reaction by α-cyclodextrin glucanotransferase (α- CGTase) from recombinant Escherichia coli with L-ascorbic acid (AA) and β-cyclodextrin (β-CD) as the substrates. Liquid chromatography-tandem mass spectrometry analysis
was conducted for AA-2G identification, and the glucoamylase treatment was carried out to produce AA-2G from AA-2-oilgosaccharides.
The optimal temperature and pH for the enzymatic AA-2G production were 37°C and 5.5, respectively, and the optimal α-CGTase
concentration and substrate mass ratio (AA:β-CD) for AA-2G synthesis were 160 U/mL and 1:1, respectively. At these optimal
process conditions, maximal AA-2G production reached 13 g/L. This is the first report regarding the process optimization of
enzymatic AA-2G production by α-CGTase from recombinant E. coli. The results may be useful for the industrial scale production of AA-2G. 相似文献
998.
Cocoon sericin plays an important role in the reeling of silk and serves as a valuable biomaterial in the field of biomedicine,
skincare, and food industries; however, knowledge about cocoon sericin proteins has been limited. For a comprehensive study
on sericin, cocoons of eight varieties of silkworm of different geographic origin and with varied cocoon color were analyzed
utilizing proteomics and bioinformatics approaches. The electrophoresis pattern demonstrated some common protein bands for
all silkworm varieties and distinctive protein bands for some of those examined in the present study. The Ser2 protein, a
new Ser3 protein, and four other novel sericin proteins were identified in cocoons for the first time. Products of both Ser1
and Ser3 genes appear to be ubiquitous in the cocoon shell of Bombyx mori. In addition, cocoons with especially high-reelability produced by the mutant strain B84 had an unique protein product of
the Ser2 gene, indicating that the protein may play an important role in cocoon reelability. A series of sequence conflicts and post-translational
modifications (PTMs) were also revealed in sericin proteins. Lipid modifications of sericin proteins, which promote waterproofing
of the cocoon shell, were observed. Further, hydroxylation was identified, which provided evidence for intermolecular bonds
among neighboring molecules of sericin as found in collagens. The sericin proteome data obtained from this study illuminated
the molecular complexity of cocoon sericin and contributed to our understanding of the properties of sericin in filature and
biomaterials. 相似文献
999.
1000.