全文获取类型
收费全文 | 414篇 |
免费 | 28篇 |
出版年
2022年 | 2篇 |
2021年 | 3篇 |
2020年 | 6篇 |
2019年 | 9篇 |
2018年 | 13篇 |
2017年 | 3篇 |
2016年 | 13篇 |
2015年 | 7篇 |
2014年 | 16篇 |
2013年 | 22篇 |
2012年 | 22篇 |
2011年 | 27篇 |
2010年 | 19篇 |
2009年 | 28篇 |
2008年 | 30篇 |
2007年 | 45篇 |
2006年 | 31篇 |
2005年 | 27篇 |
2004年 | 31篇 |
2003年 | 23篇 |
2002年 | 30篇 |
2001年 | 3篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1998年 | 4篇 |
1997年 | 4篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1993年 | 4篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1983年 | 1篇 |
1918年 | 1篇 |
排序方式: 共有442条查询结果,搜索用时 421 毫秒
41.
Green leafy volatiles or isoprenoids are produced after mechanical wounding or pathogen/herbivore attacks in higher plants. We monitored expression profiles of the genes involved in defense responses upon exposing Arabidopsis thaliana to the volatiles. Among the genes investigated, those known to be induced by mechanical wounding and/or jasmonate application, such as chalcone synthase (CHS), caffeic acid-O-methyltransferase (COMT), diacylglycerol kinase1 (DGK1), glutathione-S-transferase1 (GST1) and lipoxygenase2 (LOX2), were shown to be induced with (E)-2-hexenal, (Z)-3-hexenal, (Z)-3-hexenol or allo-ocimene (2,6-dimethyl-2,4,6-octatriene). A salicylic acid-responsive gene, pathogenesis-related protein2 (PR2), was not induced by the volatiles. Detailed analyses of the expression profiles showed that the manner of induction varied depending on either the gene monitored or the volatile used. A chemically inert compound, (Z)-3-hexenol, was also potent, which suggested that chemical reactivity was not the sole requisite for the inducing activity. With a jasmonate-insensitive mutant (jar1), the induction by the volatiles was mostly suppressed, however, that of LOX2 was unaltered. An ethylene-insensitive mutant (etr1) showed responses almost identical to the wild type, with minor exceptions. From these observations, it was suggested that both the jasmonate-dependent and -independent pathways were operative upon perception of the volatiles, while the ETR1-dependent pathway was not directly involved. When Botrytis cinerea was inoculated after the volatile treatment, retardation of disease development could be seen. It appears that volatile treatment could make the plants more resistant against the fungal disease. 相似文献
42.
43.
Sakuraba Y Sezutsu H Takahasi KR Tsuchihashi K Ichikawa R Fujimoto N Kaneko S Nakai Y Uchiyama M Goda N Motoi R Ikeda A Karashima Y Inoue M Kaneda H Masuya H Minowa O Noguchi H Toyoda A Sakaki Y Wakana S Noda T Shiroishi T Gondo Y 《Biochemical and biophysical research communications》2005,336(2):609-616
The large-scale mouse mutagenesis with ENU has provided forward-genetic resources for functional genomics. The frozen sperm archive of ENU-mutagenized generation-1 (G1) mice could also provide a "mutant mouse library" that allows us to conduct reverse genetics in any particular target genes. We have archived frozen sperm as well as genomic DNA from 9224 G1 mice. By genome-wide screening of 63 target loci covering a sum of 197 Mbp of the mouse genome, a total of 148 ENU-induced mutations have been directly identified. The sites of mutations were primarily identified by temperature gradient capillary electrophoresis method followed by direct sequencing. The molecular characterization revealed that all the identified mutations were point mutations and mostly independent events except a few cases of redundant mutations. The base-substitution spectra in this study were different from those of the phenotype-based mutagenesis. The ENU-based gene-driven mutagenesis in the mouse now becomes feasible and practical. 相似文献
44.
Takahashi M Kojima M Nakajima K Suzuki-Migishima R Motegi Y Yokoyama M Takeuchi T 《Biochemical and biophysical research communications》2004,324(4):1319-1323
jumonji (jmj) mutant mice, obtained by a gene trap strategy, showed several morphological abnormalities including neural tube and cardiac defects, and died in utero around embryonic day 11.5 (E11.5). It is unknown what causes the embryonic lethality. Here, we demonstrate that exogenous expression of jmj gene in the heart of jmj mutant mice rescued the morphological phenotypes in the heart, and these embryos survived until E13.5. These results suggest that there are at least two lethal periods in jmj mutant mice, and that cardiac abnormalities may cause the earlier lethality. In addition, the rescue of the cardiac abnormalities by the jmj transgene provided solid evidence that the cardiac abnormalities resulted from mutation of the jmj gene. 相似文献
45.
Inhibition of c-Jun NH2-terminal kinase activity improves ischemia/reperfusion injury in rat lungs 总被引:7,自引:0,他引:7
Ishii M Suzuki Y Takeshita K Miyao N Kudo H Hiraoka R Nishio K Sato N Naoki K Aoki T Yamaguchi K 《Journal of immunology (Baltimore, Md. : 1950)》2004,172(4):2569-2577
Although c-Jun NH(2)-terminal kinase (JNK) has been implicated in the pathogenesis of transplantation-induced ischemia/reperfusion (I/R) injury in various organs, its significance in lung transplantation has not been conclusively elucidated. We therefore attempted to measure the transitional changes in JNK and AP-1 activities in I/R-injured lungs. Subsequently, we assessed the effects of JNK inhibition by the three agents including SP600125 on the degree of lung injury assessed by means of various biological markers in bronchoalveolar lavage fluid and histological examination including detection of apoptosis. In addition, we evaluated the changes in p38, extracellular signal-regulated kinase, and NF-kappaB-DNA binding activity. I/R injury was established in the isolated rat lung preserved in modified Euro-Collins solution at 4 degrees C for 4 h followed by reperfusion at 37 degrees C for 3 h. We found that AP-1 was transiently activated during ischemia but showed sustained activation during reperfusion, leading to significant lung injury and apoptosis. The change in AP-1 was generally in parallel with that of JNK, which was activated in epithelial cells (bronchial and alveolar), alveolar macrophages, and smooth muscle cells (bronchial and vascular) on immunohistochemical examination. The change in NF-kappaB qualitatively differed from that of AP-1. Protein leakage, release of lactate dehydrogenase and TNF-alpha into bronchoalveolar lavage fluid, and lung injury were improved, and apoptosis was suppressed by JNK inhibition. In conclusion, JNK plays a pivotal role in mediating lung injury caused by I/R. Therefore, inhibition of JNK activity has potential as an effective therapeutic strategy for preventing I/R injury during lung transplantation. 相似文献
46.
Repression of tax expression is associated both with resistance of human T-cell leukemia virus type 1-infected T cells to killing by tax-specific cytotoxic T lymphocytes and with impaired tumorigenicity in a rat model 总被引:2,自引:0,他引:2 下载免费PDF全文
Nomura M Ohashi T Nishikawa K Nishitsuji H Kurihara K Hasegawa A Furuta RA Fujisawa J Tanaka Y Hanabuchi S Harashima N Masuda T Kannagi M 《Journal of virology》2004,78(8):3827-3836
Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL). Although the viral transactivation factor, Tax, has been known to have apparent transforming ability, the exact function of Tax in ATL development is still not clear. To understand the role of Tax in ATL development, we introduced short-interfering RNAs (siRNAs) against Tax in a rat HTLV-1-infected T-cell line. Our results demonstrated that expression of siRNA targeting Tax successfully downregulated Tax expression. Repression of Tax expression was associated with resistance of the HTLV-1-infected T cells to Tax-specific cytotoxic-T-lymphocyte killing. This may be due to the direct effect of decreased Tax expression, because the Tax siRNA did not alter the expression of MHC-I, CD80, or CD86. Furthermore, T cells with Tax downregulation appeared to lose the ability to develop tumors in T-cell-deficient nude rats, in which the parental HTLV-1-infected cells induce ATL-like lymphoproliferative disease. These results indicated the importance of Tax both for activating host immune response against the virus and for maintaining the growth ability of infected cells in vivo. Our results provide insights into the mechanisms how the host immune system can survey and inhibit the growth of HTLV-1-infected cells during the long latent period before the onset of ATL. 相似文献
47.
Persistent recognition of autologous virus by high-avidity CD8 T cells in chronic, progressive human immunodeficiency virus type 1 infection 总被引:9,自引:0,他引:9 下载免费PDF全文
Draenert R Verrill CL Tang Y Allen TM Wurcel AG Boczanowski M Lechner A Kim AY Suscovich T Brown NV Addo MM Walker BD 《Journal of virology》2004,78(2):630-641
CD8 T-cell responses are thought to be crucial for control of viremia in human immunodeficiency virus (HIV) infection but ultimately fail to control viremia in most infected persons. Studies in acute infection have demonstrated strong CD8-mediated selection pressure and evolution of mutations conferring escape from recognition, but the ability of CD8 T-cell responses that persist in late-stage infection to recognize viruses present in vivo has not been determined. Therefore, we studied 24 subjects with advanced HIV disease (median viral load = 142,000 copies/ml; median CD4 count = 71/ micro l) and determined HIV-1-specific CD8 T-cell responses to all expressed viral proteins using overlapping peptides by gamma interferon Elispot assay. Chronic-stage virus was sequenced to evaluate autologous sequences within Gag epitopes, and functional avidity of detected responses was determined. In these subjects, the median number of epitopic regions targeted was 13 (range, 2 to 39) and the median cumulative magnitude of CD8 T-cell responses was 5,760 spot-forming cells/10(6) peripheral blood mononuclear cells (range, 185 to 24,700). On average six (range, one to 8) proteins were targeted. For 89% of evaluated CD8 T-cell responses, the autologous viral sequence was predicted to be well recognized by these responses and the majority of analyzed optimal epitopes were recognized with medium to high functional avidity by the contemporary CD8 T cells. Withdrawal of antigen by highly active antiretroviral therapy led to a significant decline both in breadth (P = 0.032) and magnitude (P = 0.0098) of these CD8 T-cell responses, providing further evidence that these responses had been driven by recognition of autologous virus. These results indicate that strong, broadly directed, and high-avidity gamma-interferon-positive CD8 T-cells directed at autologous virus persist in late disease stages, and the absence of mutations within viral epitopes indicates a lack of strong selection pressure mediated by these responses. These data imply functional impairment of CD8 T-cell responses in late-stage infection that may not be reflected by gamma interferon-based screening techniques. 相似文献
48.
De Almeida Salles Perroud AP Ashimine R De Castro GM Guimarães F Vieira KP Aparecida Vilella C Samico Cavalcanti TC De Lima Zollner R 《Cytokine》2006,36(3-4):123-133
Two variants of this Walker 256 tumor have been previously reported as Walker 256 A and variant AR. The variant A has more aggressive property than variant AR and can induce systemic effects such as anorexia, sodium and water retention, followed by weight loss and death. The mechanisms involved in enhancing tumor regression and progression in this model are still incompletely understood. In the present study, serum and spleen mononuclear cells and tumor cells from animals inoculated with variants A and AR, were isolated to investigate the TGF-beta, IL-12, IFN-gamma and TNF-alpha and relationship with anemia, weight of animals, weight of spleen, volume of tumor and osmotic fragility compared with controls inoculated with Ringer Lactate. Results demonstrate that the group inoculated with variant A, compared to variant AR, shows high levels of TGF-beta gene expression in both tumor tissue and spleen cells, no expression of IFN-gamma and a progressive and higher levels of IL-12 in tumor tissue without inflammatory infiltrate visualized by optical microscopy. These results suggest that the aggressively of variant A is relate to cytokine modulation, facilitating the growth and escape of tumor cells. Furthermore, IL-12 seems to be constitutively expressed in both tumor lineage A and AR. 相似文献
49.
Rika Nagai Reina Hashimoto Yuko Tanaka Mamiko Sato Masamitsu Yamaguchi 《Experimental cell research》2010,316(2):272-285
Syntrophins are components of the dystrophin glycoprotein complex (DGC), which is encoded by causative genes of muscular dystrophies. The DGC is thought to play roles not only in linking the actin cytoskeleton to the extracellular matrix, providing stability to the cell membrane, but also in signal transduction. Because of their binding to a variety of different molecules, it has been suggested that syntrophins are adaptor proteins recruiting signaling proteins to membranes and the DGC. However, critical roles in vivo remain elusive. Drosophila Syntrophin-2 (Syn2) is an orthologue of human γ1/γ2-syntrophins. Western immunoblot analysis here showed Syn2 to be expressed throughout development, with especially high levels in the adult head. Morphological aberrations were observed in Syn2 knockdown adult flies, with lack of retinal elongation and malformation of rhabdomeres. Furthermore, Syn2 knockdown flies exhibited excessive apoptosis in third instar larvae and alterations in the actin localization in the pupal retinae. Genetic crosses with a collection of Drosophila deficiency stocks allowed us to identify seven genomic regions, deletions of which caused enhancement of the rough eye phenotype induced by Syn2 knockdown. This information should facilitate identification of Syn2 regulators in Drosophila and clarification of roles of Syn2 in eye development. 相似文献
50.
This paper reports the effect of ionic strength on the process of thermal unfolding of recombinant methionyl human granulocyte-colony stimulating factor (rmethuG-CSF) at acid pH. We previously reported that the protein aggregates were formed at the highest temperature at pD 2.1 in the pD range of 5.5-2.1 and that the aggregation proceeded a little at pD 2.1 because of the strong repulsive interaction between the unordered structures that play the role of a precursor for the aggregation. In the present study temperature-dependent IR spectra and far-UV CD spectra were measured for rmethuG-CSF in aqueous solutions containing various concentrations of NaCl at acid pH. Second derivative and curve-fitting analysis were performed to examine the obtained IR spectra. The results revealed that the structure of rmethuG-CSF becomes less stable with increasing ionic strength at all pDs investigated (pD 2.1, 2.5, and 4.0). We have also demonstrated that, at pD 2.1, the temperature at which the protein aggregation starts becomes lower and that the amount of the aggregates becomes larger with the addition of NaCl. This is probably because the addition of NaCl masks the repulsive electrostatic interaction between the unordered structures. 相似文献