全文获取类型
收费全文 | 653篇 |
免费 | 46篇 |
出版年
2022年 | 2篇 |
2021年 | 10篇 |
2020年 | 5篇 |
2019年 | 2篇 |
2018年 | 14篇 |
2017年 | 5篇 |
2016年 | 10篇 |
2015年 | 27篇 |
2014年 | 22篇 |
2013年 | 35篇 |
2012年 | 29篇 |
2011年 | 38篇 |
2010年 | 30篇 |
2009年 | 26篇 |
2008年 | 46篇 |
2007年 | 50篇 |
2006年 | 36篇 |
2005年 | 43篇 |
2004年 | 39篇 |
2003年 | 34篇 |
2002年 | 30篇 |
2001年 | 27篇 |
2000年 | 23篇 |
1999年 | 15篇 |
1998年 | 5篇 |
1997年 | 9篇 |
1996年 | 4篇 |
1995年 | 7篇 |
1994年 | 4篇 |
1993年 | 1篇 |
1992年 | 7篇 |
1991年 | 15篇 |
1990年 | 4篇 |
1989年 | 5篇 |
1988年 | 6篇 |
1987年 | 9篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1942年 | 1篇 |
排序方式: 共有699条查询结果,搜索用时 31 毫秒
131.
Inagaki YS Etherington G Geisler K Field B Dokarry M Ikeda K Mutsukado Y Dicks J Osbourn A 《The New phytologist》2011,191(2):432-448
The first committed step in sterol biosynthesis in plants involves the cyclization of 2,3-oxidosqualene by the oxidosqualene cyclase (OSC) enzyme cycloartenol synthase. 2,3-Oxidosqualene is also a precursor for triterpene synthesis. Antimicrobial triterpenes are common in dicots, but seldom found in monocots, with the notable exception of oat. Here, through genome mining and metabolic engineering, we investigate the potential for triterpene synthesis in rice. The first two steps in the oat triterpene pathway are catalysed by a divergent OSC (AsbAS1) and a cytochrome P450 (CYP51). The genes for these enzymes form part of a metabolic gene cluster. To investigate the origins of triterpene synthesis in monocots, we analysed systematically the OSC and CYP51 gene families in rice. We also engineered rice for elevated triterpene content. We discovered a total of 12 OSC and 12 CYP51 genes in rice and uncovered key events in the evolution of triterpene synthesis. We further showed that the expression of AsbAS1 in rice leads to the accumulation of the simple triterpene, β-amyrin. These findings provide new insights into the evolution of triterpene synthesis in monocots and open up opportunities for metabolic engineering for disease resistance in rice and other cereals. 相似文献
132.
Yuki Hashimoto Wataru Saito Akio Fujiya Chikako Yoshizawa Kiriko Hirooka Shohei Mori Kousuke Noda Susumu Ishida 《PloS one》2015,10(8)
Purpose
To investigate sequential post-operative thickness changes in inner and outer retinal layers in eyes with an idiopathic macular hole (MH).Methods
Retrospective case series. Twenty-four eyes of 23 patients who had received pars plana vitrectomy (PPV) for the closure of MH were included in the study. Spectral domain optical coherence tomography C-scan was used to automatically measure the mean thickness of the inner and outer retinal layers pre-operatively and up to 6 months following surgery. The photoreceptor outer segment (PROS) length was measured manually and was used to assess its relationship with best-corrected visual acuity (BCVA).Results
Compared with the pre-operative thickness, the inner layers significantly thinned during follow-up (P = 0.02), particularly in the parafoveal (P = 0.01), but not perifoveal, area. The post-operative inner layer thinning ranged from the ganglion cell layer to the inner plexiform layer (P = 0.002), whereas the nerve fiber layer was unaltered. Outer layer thickness was significantly greater post-operatively (P = 0.002), and especially the PROS lengthened not only in the fovea but also in the parafovea (P < 0.001). Six months after surgery, BCVA was significantly correlated exclusively with the elongated foveal PROS (R = 0.42, P = 0.03), but not with any of the other thickness parameters examined.Conclusions
Following PPV for MH, retinal inner layers other than the nerve fiber layer thinned, suggestive of subclinical thickening in the inner layers where no cyst was evident pre-operatively. In contrast, retinal outer layer thickness significantly increased, potentially as a result of PROS elongation linking tightly with favorable visual prognosis in MH eyes. 相似文献133.
134.
135.
Sayaka Okuzono Masataka Ishimura Shunsuke Kanno Motoshi Sonoda Noriyuki Kaku Yoshitomo Motomura Hisanori Nishio Utako Oba Masuo Hanada Jun-ichi Fukushi Michiyo Urata Dongchon Kang Hidetoshi Takada Shouichi Ohga 《Annals of clinical microbiology and antimicrobials》2018,17(1):31
Background
Streptococcus pyogenes is an uncommon pathogen of purpura fulminans, and the pathogenesis of S. pyogenes-purpura fulminans remains unclear because of paucity of cases. We reported a pediatric case of S. pyogenes-purpura fulminans with literature review of the disease.Case presentation
A 3-year-old boy showed limping, lethargy and acral gangrene within 24 h. A diagnosis of S. pyogenes-purpura fulminans was made for bacterial isolation from throat and peripheral blood. Intensive therapy led to a survival with amputation of the left distal metatarsal bone, and normal development. The isolated M12 carried no mutation of csrS/R or rgg. Thrombophilia or immunodeficiency was excluded.Discussion
Twelve-reported cases (9 pediatric and 3 elderly) of S. pyogenes-purpura fulminans started with shock and coagulopathy. Five patients age <?8 years had no underlying disease and survived. One youngest and two immunocompromised patients died.Conclusion
Streptococcus pyogenes-acute infectious purpura fulminans is a distinctive rare form of aggressive GAS infections.136.
Maintenance of genome integrity is essential for all organisms because genome information regulates cell proliferation, growth arrest, and vital metabolic processes in cells, tissues, organs, and organisms. Because genomes are constantly exposed to intrinsic and extrinsic genotoxic stress, cellular DNA repair machinery and proper DNA damage responses (DDR) have evolved to quickly eliminate genotoxic DNA lesions, thus maintaining the genome integrity suitably. In human, germline mutations in genes involved not only in cellular DNA repair pathways but also in cellular DDR machinery frequently predispose hereditary diseases associated with chromosome aberrations. These genetic syndromes typically displaying mutations in DNA repair/DDR-related genes are often called “genome instability syndromes.” Common features of these hereditary syndromes include a high incidence of cancers and developmental abnormalities including short stature, microcephaly, and/or neurological deficiencies. However, precisely how impaired DNA repair and/or dysfunctional DDR pathologically promote(s) these syndromes are poorly understood. In this review article, we summarize the clinical symptoms of several representatives “genome instability syndromes” and propose the plausible pathogenesis thereof. 相似文献
137.
138.
Gakuro Harada Shiori Onoue Chisato Inoue Sakae Hanada Yoshinori Katakura 《Cytotechnology》2018,70(6):1707-1712
Delphinidin is an anthocyanidin commonly found in various fruits and vegetables. Delphinidin has been known to possess many functions, such as an antioxidant, and anti-inflammatory, anti-cancer and anti-muscular atrophy agent. In this study, we attempted to evaluate the effects of delphinidin on lipid accumulation in hepatocytes. The results showed that palmitic acid (PA)-induced cellular senescence in HepG2 cells and reduced the expression of SMARCD1, which is known to regulate senescence-associated lipid accumulation in hepatocytes. However, delphinidin-3-glucoside (D3 g) suppressed PA-induced senescence and reversed the expression of SMARCD1 to the level of untreated HepG2 cells. Consequently, D3 g inhibited PA-induced lipid accumulation through the restoration of the expression of SMARCD1 and fatty acid oxidation genes. Taken together, our results suggest that D3 g suppresses the lipid accumulation induced by hepatocyte senescence. 相似文献
139.
Shohei Utsumi Kousuke Sato Satoshi Ichikawa 《Bioorganic & medicinal chemistry letters》2018,28(12):2189-2194
DNA cytosine-5 methyltransferase (DNMT) catalyzes methylation at the C5 position of cytosine in the CpG sequence in double stranded DNA to give 5-methylCpG (mCpG) in the epigenetic regulation step in human cells. The entire reaction mechanism of DNMT is divided into six steps, which are scanning, recognition, flipping, loop locking, methylation, and releasing. The methylation and releasing mechanism are well-investigated; however, few reports are known about other reaction steps. To obtain insight into the reaction mechanism, we planned the incorporation of acyclic nucleosides, which make it easy to flip out the target nucleobase, into oligodeoxynucleotides (ODNs) and investigated the interaction between the ODN and DNMT. Here, we describe the design and synthesis of ODNs containing new acyclic 5-fluorocytosine nucleosides and their physiological and biological properties, including their interactions with DNMT. We found that the ODNs containing the acyclic 5-fluorocytosine nucleoside showed higher flexibility than those that contain 5-fluoro-2′-deoxycytidine. The observed flexibility of ODNs is expected to influence the scanning and recognition steps due to the decrease in helicity of the B-form. 相似文献
140.
Bodrug SE Aimé-Sempé C Sato T Krajewski S Hanada M Reed JC 《Cell death and differentiation》1995,2(3):173-182
Mcl-1 is a recently described homologue of Bcl-2 whose function and biochemical characteristics remain poorly defined. Gene transfer experiments in lnterleukin-3 (IL-3)-dependent myeloid progenitor 32D.3 cells and pro-B-lymphoid FL5.12 cells demonstrated that enforced production of high levels of Mcl-1 protein failed to prolong the survival of cells when cultured in the absence of IL-3, whereas Bcl-2 did delay cell death. Mcl-1 also did not prolong the survival in vitro of 32D.3 cells that had been induced to differentiate into mature neutrophils using Granulocyte-Colony Stimulating Factor (G-CSF), whereas Bcl-2 did. 32D.3 and FL5.12 cells co-transfected with Mcl-1 and Bcl-2 displayed survival kinetics essentially identical to cells transfected with Bcl-2 alone, when cultured in the absence of IL-3, indicating that Mcl-1 neither enhances nor impairs Bcl-2 function. In contrast to the lack of effects of Mcl-1 in 32D.3 and FL5.12 cells, Mcl-1 (like Bcl-2) was able to neutralise Bax-induced cytotoxicity in yeast (S. cerevisiae). Moreover, the recombinant GST-Mcl-1 protein bound specifically to in vitro translated Bax protein, as well as to Bax protein present in detergent lysates prepared from 32D.3 and FL5.12 cells, based on in vitro binding assays. However, Mcl-1 and Bax proteins could not be co-immunoprecipitated from control and transfected 32D.3 and FL5.12 cells, whereas Bcl-2 and Bax were easily co-immunoprecipitated under the same conditions. The findings suggest that while Mcl-1 has the capacity to bind to and neutralise the cell death promoting activity of Bax, other factors such as perhaps additional proteins or undefined post-translational modifications may influence its ability to bind to Bax in vivo and thus affect its function as a cell death blocker. 相似文献