全文获取类型
收费全文 | 24428篇 |
免费 | 1949篇 |
国内免费 | 1824篇 |
专业分类
28201篇 |
出版年
2024年 | 55篇 |
2023年 | 301篇 |
2022年 | 796篇 |
2021年 | 1285篇 |
2020年 | 886篇 |
2019年 | 1040篇 |
2018年 | 1031篇 |
2017年 | 748篇 |
2016年 | 1069篇 |
2015年 | 1467篇 |
2014年 | 1726篇 |
2013年 | 1891篇 |
2012年 | 2248篇 |
2011年 | 1925篇 |
2010年 | 1169篇 |
2009年 | 1019篇 |
2008年 | 1201篇 |
2007年 | 1064篇 |
2006年 | 921篇 |
2005年 | 810篇 |
2004年 | 693篇 |
2003年 | 628篇 |
2002年 | 544篇 |
2001年 | 481篇 |
2000年 | 417篇 |
1999年 | 403篇 |
1998年 | 255篇 |
1997年 | 269篇 |
1996年 | 256篇 |
1995年 | 242篇 |
1994年 | 220篇 |
1993年 | 136篇 |
1992年 | 206篇 |
1991年 | 145篇 |
1990年 | 130篇 |
1989年 | 109篇 |
1988年 | 73篇 |
1987年 | 94篇 |
1986年 | 56篇 |
1985年 | 56篇 |
1984年 | 43篇 |
1983年 | 30篇 |
1982年 | 30篇 |
1981年 | 19篇 |
1980年 | 8篇 |
1979年 | 6篇 |
排序方式: 共有10000条查询结果,搜索用时 8 毫秒
921.
Currently, acrylic acid is produced at a low yield by the resting cells of Clostridium propionicum with the supplement of extra electron acceptors. As an alternative way, acrylic acid production coupled with electricity generation was achieved by C. propionicum‐based microbial fuel cells (MFCs). Electricity was generated in the salt‐bridge MFCs with cysteine and resazurin in the anode chamber as mediators, and K3Fe(CN)6 as the cathode electron acceptor. Power generation was 21.78 mW/m2 with an internal resistance of 9809 Ω. Cyclic voltammograms indicated the main mechanism of power production was the electron transfer facilitated by mediators in the system. In the salt‐bridge MFC system, 0.694 mM acrylic acid was produced together with electricity generation. 相似文献
922.
The pK(a)s of 96 acids and bases introduced into buried sites in the staphylococcal nuclease protein (SNase) were calculated using the multiconformation continuum electrostatics (MCCE) program and the results compared with experimental values. The pK(a)s are obtained by Monte Carlo sampling of coupled side chain protonation and position as a function of pH. The dependence of the results on the protein dielectric constant (ε(prot)) in the continuum electrostatics analysis and on the Lennard-Jones non-electrostatics parameters was evaluated. The pK(a)s of the introduced residues have a clear dependence on ε(prot,) whereas native ionizable residues do not. The native residues have electrostatic interactions with other residues in the protein favoring ionization, which are larger than the desolvation penalty favoring the neutral state. Increasing ε(prot) scales both terms, which for these residues leads to small changes in pK(a). The introduced residues have a larger desolvation penalty and negligible interactions with residues in the protein. For these residues, changing ε(prot) has a large influence on the calculated pK(a). An ε(prot) of 8-10 and a Lennard-Jones scaling of 0.25 is best here. The X-ray crystal structures of the mutated proteins are found to provide somewhat better results than calculations carried out on mutations made in silico. Initial relaxation of the in silico mutations by Gromacs and extensive side chain rotamer sampling within MCCE can significantly improve the match with experiment. 相似文献
923.
To study the roles of microRNA-223 (miR-223) in regulation of cell growth, we established a miR-223 over-expression model in HeLa cells infected with miR-223 by Lentivirus pLL3.7 system. We observed in this model that miR-223 significantly suppressed the proliferation, growth rate, colony formation of HeLa cells in vitro, and in vivo tumorigenicity or tumor formation in nude mice. To investigate the mechanisms involved, we scanned and examined the potential and putative target molecules of miR-223 by informatics, quantitative PCR and Western blot, and found that insulin-like growth factor-1 receptor (IGF-1R) was the functional target of miR-223 inhibition of cell proliferation. Targeting IGF-1R by miR-223 was not only seen in HeLa cells, but also in leukemia and hepatoma cells. The downstream pathway, Akt/mTOR/p70S6K, to which the signal was mediated by IGF-1R, was inhibited as well. The relative luciferase activity of the reporter containing wild-type 3'UTR(3'untranslated region) of IGF-1R was significantly suppressed, but the mutant not. Silence of IGF-1R expression by vector-based short hairpin RNA resulted in the similar inhibition with miR-223. Contrarily, rescued IGF-1R expression in the cells that over-expressed miR-223, reversed the inhibition caused by miR-223 via introducing IGF-1R cDNA that didn't contain the 3'UTR. Meanwhile, we also noted that miR-223 targeted Rasa1, but the downstream molecules mediated by Rasa1 was neither targeted nor regulated. Therefore we believed that IGF-1R was the functional target for miR-223 suppression of cell proliferation and its downstream PI3K/Akt/mTOR/p70S6K pathway suppressed by miR-223 was by targeting IGF-1R. 相似文献
924.
Huang J Morehouse C Streicher K Higgs BW Gao J Czapiga M Boutrin A Zhu W Brohawn P Chang Y Viner J LaVallee T Richman L Jallal B Yao Y 《PloS one》2011,6(10):e26177
Purpose
Insulin-like growth factor (IGF) signaling through human insulin receptor isoform A (IR-A) contributes to tumorigenesis and intrinsic resistance to anti-IGF1R therapy. In the present study, we (a) developed quantitative TaqMan real time-PCR-based assays (qRT-PCR) to measure human insulin receptor isoforms with high specificity, (b) evaluated isoform expression levels in molecularly-defined breast cancer subtypes, and (c) identified the IR-A:IR-B mRNA ratio as a potential biomarker guiding patient stratification for anti-IGF therapies.Experimental Design
mRNA expression levels of IR-A and IR-B were measured in 42 primary breast cancers and 19 matched adjacent normal tissues with TaqMan qRT-PCR assays. The results were further confirmed in 165 breast cancers. The tumor samples were profiled using whole genome microarrays and subsequently subtyped using the PAM50 breast cancer gene signature. The relationship between the IR-A:IR-B ratio and cancer subtype, as well as markers of proliferation were characterized.Results
The mRNA expression levels of IR-A in the breast tumors were similar to those observed in the adjacent normal tissues, while the mRNA levels of IR-B were significantly decreased in tumors. The IR-A:IR-B ratio was significantly higher in luminal B breast cancer than in luminal A. Strong concordance between the IR-A:IR-B ratio and the composite Oncotype DX proliferation score was observed for stratifying the latter two breast cancer subtypes.Conclusions
The reduction in IR-B expression is the key to the altered IR-A:IR-B ratio observed in breast cancer. The IR-A:IR-B ratio may have biomarker utility in guiding a patient stratification strategy for an anti-IGF therapeutic. 相似文献925.
Jiang C Mithani A Gan X Belfield EJ Klingler JP Zhu JK Ragoussis J Mott R Harberd NP 《Current biology : CB》2011,21(16):1385-1390
Multicellular organisms can be regenerated from totipotent differentiated somatic cell or nuclear founders [1-3]. Organisms regenerated from clonally related isogenic founders might a priori have been expected to be phenotypically invariant. However, clonal regenerant animals display variant phenotypes caused by defective epigenetic reprogramming of gene expression [2], and clonal regenerant plants exhibit poorly understood heritable phenotypic ("somaclonal") variation [4-7]. Here we show that somaclonal variation in regenerant Arabidopsis lineages is associated with genome-wide elevation in DNA sequence mutation rate. We also show that regenerant mutations comprise?a distinctive molecular spectrum of base substitutions, insertions, and deletions that probably results from decreased DNA repair fidelity. Finally, we show that while regenerant base substitutions are a likely major genetic cause of the somaclonal variation of regenerant Arabidopsis lineages, transposon movement is unlikely to contribute substantially to that variation. We conclude that the phenotypic variation of regenerant plants, unlike that of regenerant animals, is substantially due to DNA sequence mutation. 相似文献
926.
Fabrication of biomass materials by a microwave-assisted method in ionic liquids allows the high value-added applications of biomass by combining three major green chemistry principles: using environmentally preferable solvents, using an environmentally friendly method, and making use of renewable biomass materials. Herein, we report a rapid and green microwave-assisted method for the synthesis of the cellulose/calcium silicate nanocomposites in ionic liquids and recycled ionic liquids. These calcium silicate nanoparticles or nanosheets as prepared were homogeneously dispersed in the cellulose matrix. The experimental results confirm that the ionic liquids can be used repeatedly. Of course, the slight differences were also observed using ionic liquids and recycled ionic liquids. Compared with other conventional methods, the rapid, green, and environmentally friendly microwave-assisted method in ionic liquids opens a new window to the high value-added applications of biomass. 相似文献
927.
目的:从分子水平探讨黄精属部分药用植物间的系统位置。方法:采用RAPD分子标记方法,以同科万寿竹属植物宝铎草(Disporum sessile D.Don)为外类群,对百合科黄精属19批(6种)药用植物进行基因组DNA的多态性分析,通过聚类分析探讨黄精种属间亲缘关系。结果:筛选出7条随机引物,聚类结果表明,黄精属植物在属级分类上特征明显,但属内分类有交叉。结论:RAPD技术可以为黄精属的分类和种的鉴别提供一定的理论依据。 相似文献
928.
Xuan SQ Zheng JY Wang H Gao P Zhou SB Liu K Zhu GP 《Genetics and molecular research : GMR》2011,10(4):3141-3145
Lycoris radiata is a perennial herb that has been used in traditional Chinese medicine for a long time and has two main medicinal components in its bulb, lycorine and galanthamine. However, the original microsatellite loci have not been developed for any species of Lycoris. Total genomic DNA was extracted from fresh bulbs using a modified CTAB protocol. We isolated 10 microsatellite loci from 21 L. radiata individuals of a natural population from Yellow Mountain in Anhui Province, China. The number of alleles ranged from two to nine. The observed and expected heterozygosities ranged from 0.238 to 0.952 and from 0.455 to 0.784, respectively. One locus significantly deviated from Hardy-Weinberg equilibrium and no significant linkage disequilibrium was found between pairs of loci. Cross-species amplification of these microsatellite loci was characterized in additional five species (L. sprengeri, L. anhuiensis, L. albiflora, L. longituba, and L. chinensis) of Lycoris. The results suggest that these microsatellite markers would contribute to the population genetic studies of L. radiata and other related species. 相似文献
929.
The Lin28/let-7 axis regulates glucose metabolism 总被引:3,自引:0,他引:3
Zhu H Shyh-Chang N Segrè AV Shinoda G Shah SP Einhorn WS Takeuchi A Engreitz JM Hagan JP Kharas MG Urbach A Thornton JE Triboulet R Gregory RI;DIAGRAM Consortium;MAGIC Investigators Altshuler D Daley GQ 《Cell》2011,147(1):81-94
The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes, while the RNA-binding proteins Lin28a/b promote malignancy by inhibiting let-7 biogenesis. We have uncovered unexpected roles for the Lin28/let-7 pathway in regulating metabolism. When overexpressed in mice, both Lin28a and LIN28B promote an insulin-sensitized state that resists high-fat-diet induced diabetes. Conversely, muscle-specific loss of Lin28a or overexpression of let-7 results in insulin resistance and impaired glucose tolerance. These phenomena occur, in part, through the let-7-mediated repression of multiple components of the insulin-PI3K-mTOR pathway, including IGF1R, INSR, and IRS2. In addition, the mTOR inhibitor, rapamycin, abrogates Lin28a-mediated insulin sensitivity and enhanced glucose uptake. Moreover, let-7 targets are enriched for genes containing SNPs associated with type 2 diabetes and control of fasting glucose in human genome-wide association studies. These data establish the Lin28/let-7 pathway as a central regulator of mammalian glucose metabolism. 相似文献
930.
Endostatin promotes the anabolic program of rabbit chondrocyte 总被引:3,自引:0,他引:3