全文获取类型
收费全文 | 496篇 |
免费 | 64篇 |
国内免费 | 1篇 |
专业分类
561篇 |
出版年
2022年 | 4篇 |
2021年 | 5篇 |
2020年 | 7篇 |
2019年 | 7篇 |
2018年 | 8篇 |
2017年 | 6篇 |
2016年 | 7篇 |
2015年 | 10篇 |
2014年 | 13篇 |
2013年 | 16篇 |
2012年 | 32篇 |
2011年 | 38篇 |
2010年 | 20篇 |
2009年 | 8篇 |
2008年 | 31篇 |
2007年 | 25篇 |
2006年 | 26篇 |
2005年 | 29篇 |
2004年 | 21篇 |
2003年 | 22篇 |
2002年 | 36篇 |
2001年 | 4篇 |
2000年 | 9篇 |
1999年 | 4篇 |
1998年 | 5篇 |
1997年 | 5篇 |
1996年 | 4篇 |
1995年 | 7篇 |
1994年 | 7篇 |
1993年 | 6篇 |
1992年 | 7篇 |
1991年 | 4篇 |
1990年 | 8篇 |
1989年 | 6篇 |
1988年 | 7篇 |
1987年 | 4篇 |
1986年 | 8篇 |
1985年 | 5篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 6篇 |
1981年 | 9篇 |
1978年 | 4篇 |
1977年 | 7篇 |
1976年 | 8篇 |
1975年 | 5篇 |
1974年 | 5篇 |
1973年 | 7篇 |
1971年 | 4篇 |
1965年 | 4篇 |
排序方式: 共有561条查询结果,搜索用时 12 毫秒
431.
Background
Genetic reassortment plays a critical role in the generation of pandemic strains of influenza virus. The influenza virus RNA polymerase, composed of PB1, PB2 and PA subunits, has been suggested to influence the efficiency of genetic reassortment. However, the role of the RNA polymerase in the genetic reassortment is not well understood.Methodology/Principal Findings
Here, we reconstituted reassortant ribonucleoprotein (RNP) complexes, and demonstrated that the PB2 subunit of A/HongKong/156/1997 (H5N1) [HK PB2] dramatically reduced the synthesis of mRNA, cRNA and vRNA when introduced into the polymerase of other influenza strains of H1N1 or H3N2. The HK PB2 had no significant effect on the assembly of the polymerase trimeric complex, or on promoter binding activity or replication initiation activity in vitro. However, the HK PB2 was found to remarkably impair the accumulation of RNP. This impaired accumulation and activity of RNP was fully restored when four amino acids at position 108, 508, 524 and 627 of the HK PB2 were mutated.Conclusions/Significance
Overall, we suggest that the PB2 subunit of influenza polymerase might play an important role for the replication of reassortant ribonucleoprotein complexes. 相似文献432.
Mase K Mizuno T Ishihama N Fujii T Mori H Kodama M Yoshioka H 《Molecular plant-microbe interactions : MPMI》2012,25(8):1015-1025
Programmed cell death (PCD), known as hypersensitive response cell death, has an important role in plant defense response. The signaling pathway of PCD remains unknown. We employed AAL toxin and Nicotiana umbratica to analysis plant PCD. AAL toxin is a pathogenicity factor of the necrotrophic pathogen Alternaria alternata f. sp. lycopersici. N. umbratica is sensitive to AAL toxin, susceptible to pathogens, and effective in Tobacco rattle virus-based virus-induced gene silencing (VIGS). VIGS analyses indicated that AAL toxin-triggered cell death (ACD) is dependent upon the mitogen-activated protein (MAP) kinase kinase MEK2, which is upstream of both salicylic acid-induced protein kinase (SIPK) and wound-induced protein kinase (WIPK) responsible for ethylene (ET) synthesis. ET treatment of MEK2-silenced N. umbratica re-established ACD. In SIPK- and WIPK-silenced N. umbratica, ACD was compromised and ET accumulation was not observed. However, in contrast to the case of MEK2-silenced plants, ET treatment did not induce cell death in SIPK- and WIPK-silenced plants. This work showed that ET-dependent pathway and MAP kinase cascades are required in ACD. Our results suggested that MEK2-SIPK/WIPK cascades have roles in ET biosynthesis; however, SIPK and WIPK have other roles in ET signaling or another pathway leading to cell death by AAL toxin. 相似文献
433.
Nakamura N Yamauchi T Hiramoto M Yuri M Naito M Takeuchi M Yamanaka K Kita A Nakahara T Kinoyama I Matsuhisa A Kaneko N Koutoku H Sasamata M Yokota H Kawabata S Furuichi K 《Molecular & cellular proteomics : MCP》2012,11(7):M111.013243-M111.013243-6
434.
Konno M Shirakawa H Miyake T Sakimoto S Nakagawa T Kaneko S 《Biochemical and biophysical research communications》2012,417(2):784-789
Store-operated channels (SOC) are Ca(2+)-permeable channels that are activated by IP(3)-receptor-mediated Ca(2+) depletion of the endoplasmic reticulum (ER). Recent studies identify a membrane pore subunits, Orai1 and a Ca(2+) sensor on ER, STIM1 as components of Ca(2+) release-activated Ca(2+) (CRAC) channels, which are well-characterized SOCs. On the other hand, proteins that act as modulators of SOC activity remain to be identified. Calumin is a Ca(2+)-binding protein that resides on the ER and functional experiments using calumin-null mice demonstrate that it is involved in SOC function, although its role is unknown. This study used electrophysiological analysis to explore whether calumin modulates CRAC channel activity. CRAC channel currents were absent in HEK293 cells co-expressing calumin with the CRAC channel components, Orai1 or STIM1. Meanwhile, HEK cells that co-expressed calumin with CRAC channels exhibited larger currents with slower inactivation than cells expressing CRAC channels alone. The current-voltage relationship showed an inwardly rectifying current, but a negative shift in the reversal potential of greater than 60mV was observed in HEK cells co-expressing calumin with CRAC channels. In addition, the permeability coefficient ratio of Ca(2+) over monovalent cations was much lower than that of cells expressing CRAC channels alone. Replacement of Na(+) with N-methyl-d-glucamine(+) in the external solution noticeably diminished the CRAC current in HEK cells co-expressing calumin and CRAC channels. In a Cs(+)-based external solution, CRAC current was not observed in either cell-type. In addition, Ca(2+) imaging analysis revealed that co-transfection of calumin reduced extracellular Ca(2+) influx via CRAC channels. Further, calumin was shown to be directly associated with CRAC channels. These results reveal a novel mechanism for the regulation of CRAC channels by calumin. 相似文献
435.
Li J Koike J Kugoh H Arita M Ohhira T Kikuchi Y Funahashi K Takamatsu K Boland CR Koi M Hemmi H 《Biochimica et biophysica acta》2012,1823(4):889-899
Down-regulation of hMSH3 is associated with elevated microsatellite alterations at selected tetranucleotide repeats and low levels of microsatellite instability in colorectal cancer (CRC). However, the mechanism that down-regulates hMSH3 in CRC is not known. In this study, a significant association between over-expression of glucose transporter 1, a marker for hypoxia, and down-regulation of hMSH3 in CRC tissues was observed. Therefore, we examined the effect of hypoxia on the expression of hMSH3 in human cell lines. When cells with wild type p53 (wt-p53) were exposed to hypoxia, rapid down-regulation of both hMSH2 and hMSH3 occurred. In contrast, when null or mutated p53 (null/mut-p53) cells were exposed to hypoxia, only hMSH3 was down-regulated, and at slower rate than wt-p53 cells. Using a reporter assay, we found that disruption of the two putative hypoxia response elements (HREs) located within the promoter region of the hMSH3 abrogated the suppressive effect of hypoxia on reporter activity regardless of p53 status. In an EMSA, two different forms of HIF-1α complexes that specifically bind to these HREs were detected. A larger complex containing HIF-1α predominantly bound to the HREs in hypoxic null/mut-p53 cells whereas a smaller complex predominated in wt-p53 cells. Finally, HIF-1α knockdown by siRNA significantly inhibited down-regulation of hMSH3 by hypoxia in both wt-p53 and mut-p53 cells. Taken together, our results suggest that the binding of HIF-1α complexes to HRE sites is necessary for down-regulation of hMSH3 in both wt-p53 and mut-p53 cells. 相似文献
436.
437.
Although the role of aromatase in many estrogen-dependent reproductive and metabolic functions is well documented in vertebrates,
its involvement in the ovarian development of species exhibiting temperature-dependent sex determination (TSD) is incompletely
understood. This is partly due to the conflicting temporal and spatial pattern of aromatase expression and activity across taxa. To help resolve this ongoing debate, we compared for the first time the embryological
ontogeny of aromatase expression in turtles possessing genotypic sex determination (GSD) (Apalone mutica) and TSD (Chrysemys picta) incubated under identical conditions. As anticipated, we found no significant thermal differences in aromatase expression at any stage examined (prior to until the end of the thermosensitive period) in A. mutica. Surprisingly, the same was true for C. picta. When placed in a phylogenetic context, our results suggest that aromatase expression is evolutionarily plastic with respect to sex determination in reptiles, and that differences between reptilian
TSD and GSD are not aromatase-driven. Further research across TSD and GSD species is warranted to fully decipher the evolution of functional differences
among sex-determining mechanisms. 相似文献
438.
Furutani M Kajiwara T Kato T Treml BS Stockum C Torres-Ruiz RA Tasaka M 《Development (Cambridge, England)》2007,134(21):3849-3859
Intercellular transport of the phytohormone auxin is a significant factor for plant organogenesis. To investigate molecular mechanisms by which auxin controls organogenesis, we analyzed the macchi-bou 4 (mab4) mutant identified as an enhancer of pinoid (pid). Although mab4 and pid single mutants displayed relatively mild cotyledon phenotypes, pid mab4 double mutants completely lacked cotyledons. We found that MAB4 was identical to ENHANCER OF PINOID (ENP), which has been suggested to control PIN1 polarity in cotyledon primordia. MAB4/ENP encodes a novel protein, which belongs to the NON-PHOTOTROPIC HYPOCOTYL 3 (NPH3) family thought to function as a signal transducer in phototropism and control lateral translocation of auxin. MAB4/ENP mRNA was detected in the protodermal cell layer of the embryo and the meristem L1 layer at the site of organ initiation. In the mab4 embryo, the abundance of PIN1:GFP was severely decreased at the plasma membrane in the protodermal cell layer. In addition, subcellular localization analyses indicated that MAB4/ENP resides on a subpopulation of endosomes as well as on unidentified intracellular compartments. These results indicate that MAB4/ENP is involved in polar auxin transport in organogenesis. 相似文献
439.
The number of repeat in the microsatellite region (AATG)(5-14) of the human thyroid peroxidase gene (TOPX) was determined using an automated DNA analysis system with nano-scale engineered biomagnetite. Thermal melting curve analysis of DNA duplexes on biomagnetite indicated that shorter repeat sequences (less than 9 repeats) were easily discriminated. However, it was difficult to determine the number of repeats at more than nine. In order to improve the selectivity of this method for the longer repeats, a "double probe hybridization assay" was performed in which an intermediate probe was used to replace a target repeat sequence having more than 9 repeats with a shorter sequence possessing less than 9 repeats. Thermal probe melting curve analyses and Tm determination confirmed that the target with 10 repeats was converted to 5 repeats, 11 repeats converted to 4 and 12 to 3, respectively. Furthermore, rapid determination of repeat numbers was possible by measuring fluorescence intensities obtained by probe dissociation at 56 and 66 degrees C, and 40, 60 and 80 degrees C for signal normalization. 相似文献
440.