全文获取类型
收费全文 | 154篇 |
免费 | 11篇 |
专业分类
165篇 |
出版年
2021年 | 2篇 |
2020年 | 2篇 |
2018年 | 2篇 |
2017年 | 2篇 |
2016年 | 5篇 |
2015年 | 7篇 |
2014年 | 5篇 |
2013年 | 6篇 |
2012年 | 4篇 |
2011年 | 4篇 |
2010年 | 2篇 |
2009年 | 6篇 |
2008年 | 5篇 |
2007年 | 6篇 |
2006年 | 5篇 |
2005年 | 4篇 |
2004年 | 5篇 |
2003年 | 3篇 |
2002年 | 4篇 |
2001年 | 7篇 |
2000年 | 4篇 |
1999年 | 6篇 |
1998年 | 10篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 6篇 |
1994年 | 2篇 |
1993年 | 4篇 |
1992年 | 6篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1986年 | 4篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 4篇 |
1977年 | 2篇 |
1975年 | 3篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1966年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有165条查询结果,搜索用时 15 毫秒
11.
Luaine Bandounas Nick JP Wierckx Johannes H de Winde Harald J Ruijssenaars 《BMC biotechnology》2011,11(1):1-11
Background
The number of biotransformations that use nicotinamide recycling systems is exponentially growing. For this reason one of the current challenges in biocatalysis is to develop and optimize more simple and efficient cofactor recycling systems. One promising approach to regenerate NAD+ pools is the use of NADH-oxidases that reduce oxygen to hydrogen peroxide while oxidizing NADH to NAD+. This class of enzymes may be applied to asymmetric reduction of prochiral substrates in order to obtain enantiopure compounds.Results
The NADH-oxidase (NOX) presented here is a flavoenzyme which needs exogenous FAD or FMN to reach its maximum velocity. Interestingly, this enzyme is 6-fold hyperactivated by incubation at high temperatures (80°C) under limiting concentrations of flavin cofactor, a change that remains stable even at low temperatures (37°C). The hyperactivated form presented a high specific activity (37.5 U/mg) at low temperatures despite isolation from a thermophile source. Immobilization of NOX onto agarose activated with glyoxyl groups yielded the most stable enzyme preparation (6-fold more stable than the hyperactivated soluble enzyme). The immobilized derivative was able to be reactivated under physiological conditions after inactivation by high solvent concentrations. The inactivation/reactivation cycle could be repeated at least three times, recovering full NOX activity in all cases after the reactivation step. This immobilized catalyst is presented as a recycling partner for a thermophile alcohol dehydrogenase in order to perform the kinetic resolution secondary alcohols.Conclusion
We have designed, developed and characterized a heterogeneous and robust biocatalyst which has been used as recycling partner in the kinetic resolution of rac-1-phenylethanol. The high stability along with its capability to be reactivated makes this biocatalyst highly re-useable for cofactor recycling in redox biotransformations. 相似文献12.
Isabelle Vanessa Mohrenz Patrick Antonietti Stefan Pusch David Capper Jörg Balss Sophia Voigt Susanne Weissert Alicia Mukrowsky Jan Frank Christian Senft Volker Seifert Andreas von Deimling Donat Kögel 《Apoptosis : an international journal on programmed cell death》2013,18(11):1416-1425
Isocitrate dehydrogenase 1 (IDH1) decarboxylates isocitrate to α-ketoglutarate (α-KG) leading to generation of NADPH, which is required to regenerate reduced glutathione (GSH), the major cellular ROS scavenger. Mutation of R132 of IDH1 abrogates generation of α-KG and leads to conversion of α-KG to 2-hydroxyglutarate. We hypothesized that glioma cells expressing mutant IDH1 have a diminished antioxidative capacity and therefore may encounter an ensuing loss of cytoprotection under conditions of oxidative stress. Our study was performed with LN229 cells stably overexpressing IDH1 R132H and wild type IDH1 or with a lentiviral IDH1 knockdown. Quantification of GSH under basal conditions and following treatment with the glutathione reductase inhibitor BCNU revealed significantly lower GSH levels in IDH1 R132H expressing cells and IDH1 KD cells compared to their respective controls. FACS analysis of cell death and ROS production also demonstrated an increased sensitivity of IDH1-R132H-expressing cells and IDH1 KD cells to BCNU, but not to temozolomide. The sensitivity of IDH1-R132H-expressing cells and IDH1 KD cells to ROS induction and cell death was further enhanced with the transaminase inhibitor aminooxyacetic acid and under glutamine free conditions, indicating that these cells were more addicted to glutaminolysis. Increased sensitivity to BCNU-induced ROS production and cell death was confirmed in HEK293 cells inducibly expressing the IDH1 mutants R132H, R132C and R132L. Based on these findings we propose that in addition to its established pro-tumorigenic effects, mutant IDH1 may also limit the resistance of gliomas to specific death stimuli, therefore opening new perspectives for therapy. 相似文献
13.
Cassava is infected by numerous geminiviruses in Africa and India that cause devastating losses to poor farmers. We here describe the molecular diversity of seven representative cassava mosaic geminiviruses (CMGs) infecting cassava from multiple locations in Tanzania. We report for the first time the presence of two isolates in East Africa: (EACMCV-[TZ1] and EACMCV-[TZ7]) of the species East African cassava mosaic Cameroon virus, originally described in West Africa. The complete nucleotide sequence of EACMCV-[TZ1] DNA-A and DNA-B components shared a high overall sequence identity to EACMCV-[CM] components (92% and 84%). The EACMCV-[TZ1] and -[TZ7] genomic components have recombinations in the same genome regions reported in EACMCV-[CM], but they also have additional recombinations in both components. Evidence from sequence analysis suggests that the two strains have the same ancient origin and are not recent introductions. EACMCV-[TZ1] occurred widely in the southern part of the country. Four other CMG isolates were identified: two were close to the EACMV-Kenya strain (named EACMV-[KE/TZT] and EACMV-[KE/TZM] with 96% sequence identity); one isolate, TZ10, had 98% homology to EACMV-UG2Svr and was named EACMV-UG2 [TZ10]; and finally one isolate was 95% identical to EACMV-[TZ] and named EACMV-[TZ/YV]. One isolate of African cassava mosaic virus with 97% sequence identity with other isolates of ACMV was named ACMV-[TZ]. It represents the first ACMV isolate from Tanzania to be sequenced. The molecular variability of CMGs was also evaluated using partial B component nucleotide sequences of 13 EACMV isolates from Tanzania. Using the sequences of all CMGs currently available, we have shown the presence of a number of putative recombination fragments that are more prominent in all components of EACMV than in ACMV. This new knowledge about the molecular CMG diversity in East Africa, and in Tanzania in particular, has led us to hypothesize about the probable importance of this part of Africa as a source of diversity and evolutionary change both during the early stages of the relationship between CMGs and cassava and in more recent times. The existence of multiple CMG isolates with high DNA genome diversity in Tanzania and the molecular forces behind this diversity pose a threat to cassava production throughout the African continent. 相似文献
14.
15.
Margaret?O?Nwagwu Helen?Baines Jeffrey?B?Kerr Francis?JP?EblingEmail author 《Reproductive biology and endocrinology : RB&E》2005,3(1):48
Background
Testicular development is arrested in the hypogonadal (hpg) mouse due to a congenital deficiency in hypothalamic gonadotropin-releasing hormone (GnRH) synthesis. Chronic treatment of male hpg mice with estradiol induces FSH synthesis and secretion, and causes testicular maturation and qualitatively normal spermatogenesis. As estradiol negative feedback normally inhibits FSH production in the male, this study tested whether this paradoxical response to estradiol in the male hpg mouse might be due to inadequate masculinisation or incomplete defeminization in the neonatal period. Previous studies have demonstrated that treatment of hpg mice with testosterone propionate in the immediate neonatal period is necessary to allow full reproductive behaviors to be expressed following suitable endocrine stimulation at adult ages. 相似文献16.
Alexandra Kukat Eduard Hofsetz Hendrik Nolte Katharina Senft Christina Becker Benedetta Ruzzenente Hue‐Tran Hornig‐Do Rolf Wibom Rudolf J Wiesner Marcus Krüger Aleksandra Trifunovic 《The EMBO journal》2016,35(23):2566-2583
Despite being one of the most studied proteases in bacteria, very little is known about the role of ClpXP in mitochondria. We now present evidence that mammalian CLPP has an essential role in determining the rate of mitochondrial protein synthesis by regulating the level of mitoribosome assembly. Through a proteomic approach and the use of a catalytically inactive CLPP, we produced the first comprehensive list of possible mammalian ClpXP substrates involved in the regulation of mitochondrial translation, oxidative phosphorylation, and a number of metabolic pathways. We further show that the defect in mitoribosomal assembly is a consequence of the accumulation of ERAL1, a putative 12S rRNA chaperone, and novel ClpXP substrate. The presented data suggest that the timely removal of ERAL1 from the small ribosomal subunit is essential for the efficient maturation of the mitoribosome and a normal rate of mitochondrial translation. 相似文献
17.
Loss of CLPP alleviates mitochondrial cardiomyopathy without affecting the mammalian UPRmt 下载免费PDF全文
Dominic Seiferling Karolina Szczepanowska Christina Becker Katharina Senft Steffen Hermans Priyanka Maiti Tim König Alexandra Kukat Aleksandra Trifunovic 《EMBO reports》2016,17(7):953-964
The mitochondrial matrix protease CLPP plays a central role in the activation of the mitochondrial unfolded protein response (UPRmt) in Caenorhabditis elegans. Far less is known about mammalian UPRmt signaling, although similar roles were assumed for central players, including CLPP. To better understand the mammalian UPRmt signaling, we deleted CLPP in hearts of DARS2‐deficient animals that show robust induction of UPRmt due to strong dysregulation of mitochondrial translation. Remarkably, our results clearly show that mammalian CLPP is neither required for, nor it regulates the UPRmt in mammals. Surprisingly, we demonstrate that a strong mitochondrial cardiomyopathy and diminished respiration due to DARS2 deficiency can be alleviated by the loss of CLPP, leading to an increased de novo synthesis of individual OXPHOS subunits. These results question our current understanding of the UPRmt signaling in mammals, while introducing CLPP as a possible novel target for therapeutic intervention in mitochondrial diseases. 相似文献
18.
A Plonquet S Bastuji-Garin F Tahmasebi C Brisacier K Ledudal JP Farcet E Paillaud 《Immunity & ageing : I & A》2011,8(1):1-7
Background
Nosocomial infections are extremely common in the elderly and may be related to ageing of the immune system. The Immune Risk Phenotype (IRP), which predicts shorter survival in elderly patients, has not been evaluated as a possible risk factor for nosocomial infection. Our aim was to assess the prevalence of nosocomial infections in elderly in-patients and to investigate potential relationships between nosocomial infections and the immunophenotype, including IRP parameters.Results
We included 252 consecutive in-patients aged 70 years or over (mean age, 85 ± 6.2 years), between 2006 and 2008. Among them, 97 experienced nosocomial infections, yielding a prevalence rate of 38.5% (95% confidence interval, 32.5-44.5). The main infection sites were the respiratory tract (21%) and urinary tract (17.1%) When we compared immunological parameters including cell counts determined by flow cytometry in the groups with and without nosocomial infections, we found that the group with nosocomial infections had significantly lower values for the CD4/CD8 ratio and naive CD8 and CD4 T-cell counts and higher counts of memory CD8 T-cells with a significant increase in CD28-negative CD8-T cells. Neither cytomegalovirus status (positive in 193/246 patients) nor presence of the IRP was associated with nosocomial infections. However, nosocomial pneumonia was significantly more common among IRP-positive patients than IRP-negative patients (17/60 versus 28/180; p = 0.036).Conclusion
Immunological parameters that are easy to determine in everyday practice and known to be associated with immune system ageing and shorter survival in the elderly are also associated with an elevated risk of nosocomial pneumonia in the relatively short term. 相似文献19.
20.
Regulation of fermentative capacity and levels of glycolytic enzymes in chemostat cultures of Saccharomyces cerevisiae 总被引:1,自引:0,他引:1
Regulation of fermentative capacity was studied in chemostat cultures of two Saccharomyces cerevisiae strains: the laboratory strain CEN.PK113-7D and the industrial bakers’ yeast strain DS28911. The two strains were cultivated at a fixed dilution rate of 0.10 h−1 under various nutrient limitation regimes: aerobic and anaerobic glucose limitation, aerobic and anaerobic nitrogen limitation on glucose, and aerobic ethanol limitation. Also the effect of specific growth rate on fermentative capacity was compared in glucose-limited, aerobic cultures grown at dilution rates between 0.05 h−1 and 0.40 h−1. Biomass yields and metabolite formation patterns were identical for the two strains under all cultivation conditions tested. However, the way in which environmental conditions affected fermentative capacity (assayed off-line as ethanol production rate under anaerobic conditions) differed for the two strains. A different regulation of fermentative capacity in the two strains was also evident from the levels of the glycolytic enzymes, as determined by in vitro enzyme assays. With the exception of phosphofructokinase and pyruvate decarboxylase in the industrial strain, no clear-cut correlation between the activities of glycolytic enzymes and the fermentative capacity was found. These results emphasise the need for controlled cultivation conditions in studies on metabolic regulation in S. cerevisiae and demonstrate that conclusions from physiological studies cannot necessarily be extrapolated from one S. cerevisiae strain to the other. 相似文献