全文获取类型
收费全文 | 7731篇 |
免费 | 664篇 |
国内免费 | 890篇 |
专业分类
9285篇 |
出版年
2024年 | 41篇 |
2023年 | 164篇 |
2022年 | 352篇 |
2021年 | 546篇 |
2020年 | 398篇 |
2019年 | 464篇 |
2018年 | 407篇 |
2017年 | 329篇 |
2016年 | 381篇 |
2015年 | 554篇 |
2014年 | 654篇 |
2013年 | 622篇 |
2012年 | 781篇 |
2011年 | 638篇 |
2010年 | 419篇 |
2009年 | 331篇 |
2008年 | 327篇 |
2007年 | 306篇 |
2006年 | 237篇 |
2005年 | 214篇 |
2004年 | 147篇 |
2003年 | 114篇 |
2002年 | 135篇 |
2001年 | 104篇 |
2000年 | 73篇 |
1999年 | 78篇 |
1998年 | 66篇 |
1997年 | 50篇 |
1996年 | 44篇 |
1995年 | 36篇 |
1994年 | 48篇 |
1993年 | 25篇 |
1992年 | 22篇 |
1991年 | 25篇 |
1990年 | 25篇 |
1989年 | 26篇 |
1988年 | 17篇 |
1987年 | 20篇 |
1986年 | 17篇 |
1985年 | 10篇 |
1984年 | 7篇 |
1983年 | 6篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1973年 | 2篇 |
1970年 | 2篇 |
1968年 | 2篇 |
1953年 | 1篇 |
排序方式: 共有9285条查询结果,搜索用时 15 毫秒
101.
Jing Zhang Yang Zhou Lin Ma Shunquan Huang Ruijin Wang Rongrong Gao Youjun Wu Hongjun Shi Jun Zhang 《Biological trace element research》2013,152(2):267-274
Nickel is an important kind of metal and a necessary trace element in people’s production and livelihood; it is also a well-confirmed human carcinogen. In the past few years, researchers did a large number of studies about the molecular mechanisms of nickel carcinogenesis, and they focused on activation of proto-oncogenes and inactivation of anti-oncogenes caused by gene point mutation, gene deletion, gene amplification, DNA methylation, chromosome condensation, and so on that were induced by nickel. However, the researches on tumorigenic molecular mechanisms regulated by microRNAs (miRNAs) are rare. In this study, we established nickel-induced tumor by injecting Ni3S2 compounds to Wistar Rattus. By establishing a cDNA library of miRNA from rat muscle tumor tissue induced by Ni3S2, we found that the expression of miR-222 was significantly upregulated in tumor tissue compared with the normal tissue. As we expected, the expression levels of target genes of miR-222, CDKN1B and CDKN1C, were downregulated in the nickel-induced tumor. The same alteration of miR-222 and its target genes was also found in malignant 16HBE cells induced with Ni3S2 compounds. We conclude that miR-222 may promote cell proliferation infinitely during nickel-induced tumorigenesis in part by regulating the expression of its target genes CDKN1B and CDKN1C. Our study elucidated a novel molecular mechanism of nickel-induced tumorigenesis. 相似文献
102.
Vertebrate ankyrin-B and ankyrin-G exhibit divergent subcellular localization and function despite their high sequence and structural similarity and common origin from a single ancestral gene at the onset of chordate evolution. Previous studies of ankyrin family diversity have focused on the C-terminal regulatory domain. Here, we identify an ankyrin-B-specific linker peptide connecting the ankyrin repeat domain to the ZU52-UPA module that inhibits binding of ankyrin-B to membrane protein partners E-cadherin and neurofascin 186 and prevents association of ankyrin-B with epithelial lateral membranes as well as neuronal plasma membranes. The residues of the ankyrin-B linker required for autoinhibition are encoded by a small exon that is highly divergent between ankyrin family members but conserved in the ankyrin-B lineage. We show that the ankyrin-B linker suppresses activity of the ANK repeat domain through an intramolecular interaction, likely with a groove on the surface of the ANK repeat solenoid, thereby regulating the affinities between ankyrin-B and its binding partners. These results provide a simple evolutionary explanation for how ankyrin-B and ankyrin-G have acquired striking differences in their plasma membrane association while maintaining overall high levels of sequence similarity. 相似文献
103.
Xinzhu Meng Niklas L. P. Lundström Mats Bodin Åke Brännström 《Bulletin of mathematical biology》2013,75(1):1-23
With increasing fishing pressures having brought several stocks to the brink of collapse, there is a need for developing efficient harvesting methods that account for factors beyond merely yield or profit. We consider the dynamics and management of a stage-structured fish stock. Our work is based on a consumer-resource model which De Roos et al. (in Theor. Popul. Biol. 73, 47–62, 2008) have derived as an approximation of a physiologically-structured counterpart. First, we rigorously prove the existence of steady states in both models, that the models share the same steady states, and that there exists at most one positive steady state. Furthermore, we carry out numerical investigations which suggest that a steady state is globally stable if it is locally stable. Second, we consider multiobjective harvesting strategies which account for yield, profit, and the recovery potential of the fish stock. The recovery potential is a measure of how quickly a fish stock can recover from a major disturbance and serves as an indication of the extinction risk associated with a harvesting strategy. Our analysis reveals that a small reduction in yield or profit allows for a disproportional increase in recovery potential. We also show that there exists a harvesting strategy with yield close to the maximum sustainable yield (MSY) and profit close to that associated with the maximum economic yield (MEY). In offering a good compromise between MSY and MEY, we believe that this harvesting strategy is preferable in most instances. Third, we consider the impact of harvesting on population size structure and analytically determine the most and least harmful harvesting strategies. We conclude that the most harmful harvesting strategy consists of harvesting both adults and juveniles, while harvesting only adults is the least harmful strategy. Finally, we find that a high percentage of juvenile biomass indicates elevated extinction risk and might therefore serve as an early-warning signal of impending stock collapse. 相似文献
104.
Meng Liu Hongyan Liu Xiaocui Guan Hongxin Ai Haitao Wu Ping Liu Wei Gu Shuangquan Zhang 《Immunogenetics》2013,65(12):873-882
The interferon-γ-inducible lysosomal thiol reductase (GILT) has been demonstrated to play an important role in the processing and presentation of MHC class II-restricted antigen (Ag) by catalyzing disulfide bond reduction. In this study, a rainbow trout cDNA (designated as rGILT) was cloned and identified from Oncorhynchus mykiss. The open reading frame of rGILT consists of 759 bases encoding a protein of 253 amino acids with an estimated molecular mass of 28.23 kDa and a theoretical isoelectric point of 4.94. The rGILT exhibited a characteristic GILT signature sequence CQHGX2ECX2NX4C and CXXC motif. Phylogenetic analysis suggested that rGILT had been derived from a common ancestor with other GILT proteins. RT-PCR results showed that rGILT and rIFN-γ (rainbow trout IFN-γ) mRNA was expressed in a tissue-specific manner and obviously up-regulated in splenocytes and the cells from head kidney after induction with LPS. Recombinant rGILT fused with His6 tag was efficiently expressed in Escherichia coli BL21 (DE3) and purified by Ni-NTA affinity chromatography. Further study revealed that rGILT was capable of catalyzing the reduction of the interchain disulfide bonds from intact IgG. This study shows that rGILT may be involved in the immune response to bacteria challenge and maintain first line of innate immune defense at basal level in O. mykiss. It also provides the basis for investigating on the role of GILT using O. mykiss as an animal model for related studies. 相似文献
105.
M. H. Liu T. X. Gao H. H. Ma Z. J. Meng H. X. Yu 《Zeitschrift fur angewandte Ichthyologie》2013,29(2):474-475
This study determined the length–weight relationships of five flatfish species from the Yellow Sea and the Bohai Sea in China. Two of the species (Cynoglossus semilaevis and Verasper variegatus) had no previous length‐weight estimates. 相似文献
106.
Peiju Qiu Lingling Xu Lei Gao Meng Zhang Shixi Wang Sheng Tong Yue Sun Lijuan Zhang Tao Jiang 《Bioorganic & medicinal chemistry》2013,21(17):5012-5020
Epidermal growth factor receptor (EGFR) is an effective molecular target of anti-cancer therapies. Curcumin inhibits cancer cell growth in vitro by suppressing gene expression of EGFR and reduces tumor growth in various animal models. To overcome instable and insoluble properties of curcumin as therapeutics, we designed and synthesized six novel pyrimidine-substituted curcumin analogues with or without a hydroxyl group originally present in curcumin. The cell viability tests indicated that IC50 of the analogues containing hydroxyl group were 3 to 8-fold lower than those of the analogues without hydroxyl group in two colon cancer cell lines tested. Western blot analysis indicates the analogues containing hydroxyl group inhibited expression and tyrosine phosphorylation of EGFR. Further protein analyses showed that the analogues had anti-cellular proliferation, pro-apoptosis, and cell cycle arrest properties associated with suppressed EGFR expression. These results indicate that the hydroxyl groups in curcumin and the analogues were critical for observed biological activities. 相似文献
107.
Meng Zhang Liang Dong Zhubing Shi Shi Jiao Zhen Zhang Wenqing Zhang Guoguang Liu Cuicui Chen Miao Feng Qian Hao Wenjia Wang Mengxin Yin Yun Zhao Lei Zhang Zhaocai Zhou 《Structure (London, England : 1993)》2013,21(4):680-688
Highlights? Crystal structure of CCM3-MST4 heterodimeric complex ? Structural mechanism driving CCM3-GCKIII heterodimerization ? Conformational changes required for CCM3-GCKIII heterodimerization ? Synergistic effects of CCM3-MST4 complex on cell proliferation and migration 相似文献
108.
109.
Yu Hu Jianghong Meng Chunlei Shi Kirstin Hervin Pina M. Fratamico Xianming Shi 《Microbiological research》2013,168(3):174-182
Staphylococcal nuclease (here termed as Nuc1) is considered an important virulence factor and a unique marker widely used in the detection of Staphylococcus aureus. A second functional thermostable nuclease (here termed as Nuc2) in S. aureus was characterized after recombinant expression in Escherichia coli. Sequence alignment and phylogenetic analysis revealed that Nuc2 was a more conserved protein in the staphylococci group compared with Nuc1. Recombinant Nuc2 showed nuclease activity in the zymogram test and was able to degrade various types of nucleic acids. The optimal reaction temperature and pH for Nuc2 were 50 °C and pH 10, respectively. The enzymatic activity of Nuc2 was stimulated in the presence of Ca2+ (0.05 mM), Mg2+ (0.5 mM), dithiothreitol, β-mecaptoethanol, TritonX-100, Tween-20, and urea; however, activity decreased sharply when exposed to heavy metals such as Zn2+ and Mn2+, and in the presence of EDTA or SDS. Nuc2 showed weaker activity, lower thermostability and different sensitivity to these chemical agents compared with Nuc1, which was consistent with differences in the sequence pattern and structure predicted. Furthermore, a nuc1 and nuc2 double deletion mutant of S. aureus and respective complementation experiments suggest a major role for nuc1 in terms of thermonuclease activity in S. aureus. 相似文献
110.