全文获取类型
收费全文 | 92篇 |
免费 | 6篇 |
国内免费 | 4篇 |
出版年
2023年 | 2篇 |
2022年 | 1篇 |
2021年 | 3篇 |
2020年 | 4篇 |
2019年 | 3篇 |
2018年 | 1篇 |
2017年 | 1篇 |
2016年 | 6篇 |
2015年 | 5篇 |
2014年 | 7篇 |
2013年 | 8篇 |
2012年 | 5篇 |
2011年 | 8篇 |
2010年 | 1篇 |
2009年 | 5篇 |
2008年 | 5篇 |
2007年 | 3篇 |
2006年 | 3篇 |
2005年 | 1篇 |
2004年 | 2篇 |
2003年 | 2篇 |
2002年 | 3篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1992年 | 2篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 3篇 |
1985年 | 4篇 |
1969年 | 2篇 |
排序方式: 共有102条查询结果,搜索用时 125 毫秒
51.
Work in Xenopus laevis produced the first molecular explanation for neural specification, the default model, where inactivation of the BMP pathway in ectodermal cells changes fates from epidermal to neural. This review covers the present status of our understanding of neural specification, with emphasis on Xenopus, but including relevant facts in other model systems. While recent experiments have increased the complexity of the molecular picture, they have also provided additional support for the default model and the central position of the BMP pathway. We conclude that synergy between accumulated knowledge and technical progress will maintain Xenopus at the forefront of research in neural development. 相似文献
52.
Mutations in cobalamin or B12 trafficking genes needed for cofactor assimilation and targeting lead to inborn errors of cobalamin metabolism. The gene corresponding to one of these loci, cblD, affects both the mitochondrial and cytoplasmic pathways for B12 processing. We have demonstrated that fibroblast cell lines from patients with mutations in CblD, can dealkylate exogenously supplied methylcobalamin (MeCbl), an activity catalyzed by the CblC protein, but show imbalanced intracellular partitioning of the cofactor into the MeCbl and 5′-deoxyadenosylcobalamin (AdoCbl) pools. These results confirm that CblD functions downstream of CblC in the cofactor assimilation pathway and that it plays an important role in controlling the traffic of the cofactor between the competing cytoplasmic and mitochondrial routes for MeCbl and AdoCbl synthesis, respectively. In this study, we report the interaction of CblC with four CblD protein variants with variable N-terminal start sites. We demonstrate that a complex between CblC and CblD can be isolated particularly under conditions that permit dealkylation of alkylcobalamin by CblC or in the presence of the corresponding dealkylated and oxidized product, hydroxocobalamin (HOCbl). A weak CblC·CblD complex is also seen in the presence of cyanocobalamin. Formation of the CblC·CblD complex is observed with all four CblD variants tested suggesting that the N-terminal 115 residues missing in the shortest variant are not essential for this interaction. Furthermore, limited proteolysis of the CblD variants indicates the presence of a stable C-terminal domain spanning residues ∼116–296. Our results are consistent with an adapter function for CblD, which in complex with CblC·HOCbl, or possibly the less oxidized CblC·cob(II)alamin, partitions the cofactor between AdoCbl and MeCbl assimilation pathways. 相似文献
53.
Virtualization technology promises to provide better isolation and consolidation in traditional servers. However, with VMM (virtual machine monitor) layer getting involved, virtualization system changes the architecture of traditional software stack, bringing about limitations in resource allocating. The non-uniform VCPU (virtual CPU)-PCPU (physical CPU) mapping, deriving from both the configuration or the deployment of virtual machines and the dynamic runtime feature of applications, causes the different percentage of processor allocation in the same physical machine,and the VCPUs mapped these PCPUs will gain asymmetric performance. The guest OS, however, is agnostic to the non-uniformity. With assumption that all VCPUs have the same performance, it can carry out sub-optimal policies when allocating virtual resource for applications. Likewise, application runtime system can also make the same mistakes. Our focus in this paper is to understand the performance implications of the non-uniform VCPU-PCPU mapping in a virtualization system. Based on real measurements of a virtualization system with state of art multi-core processors running different commercial and emerging applications, we demonstrate that the presence of the non-uniform mapping has negative impacts on application’s performance predictability. This study aims to provide timely and practical insights on the problem of non-uniform VCPU mapping, when virtual machines being deployed and configured, in emerging cloud. 相似文献
54.
Kabil O Weeks CL Carballal S Gherasim C Alvarez B Spiro TG Banerjee R 《Biochemistry》2011,50(39):8261-8263
Human CBS is a PLP-dependent enzyme that clears homocysteine, gates the flow of sulfur into glutathione, and contributes to the biogenesis of H(2)S. The presence of a heme cofactor in CBS is enigmatic, and its conversion from the ferric- to ferrous-CO state inhibits enzyme activity. The low heme redox potential (-350 mV) has raised questions about the feasibility of the ferrous-CO state forming under physiological conditions. Herein, we provide the first evidence of reversible inhibition of CBS by CO in the presence of a human flavoprotein and NADPH. These data provide a mechanism for cross talk between two gas-signaling systems, CO and H(2)S, via heme-mediated allosteric regulation of CBS. 相似文献
55.
H Gao G Chakraborty AP Lee-Lim Q Mo M Decker A Vonica R Shen E Brogi AH Brivanlou FG Giancotti 《Cell》2012,150(4):764-779
The mechanistic underpinnings of metastatic dormancy and reactivation are poorly understood. A gain-of-function cDNA screen reveals that Coco, a secreted antagonist of TGF-β ligands, induces dormant breast cancer cells to undergo reactivation in the lung. Mechanistic studies indicate that Coco exerts this effect by blocking lung-derived BMP ligands. Whereas Coco enhances the manifestation of traits associated with cancer stem cells, BMP signaling suppresses it. Coco induces a discrete gene expression signature, which is strongly associated with metastatic relapse to the lung, but not to the bone or brain in patients. Experiments in mouse models suggest that these latter organs contain niches devoid of bioactive BMP. These findings reveal that metastasis-initiating cells need to overcome organ-specific antimetastatic signals in order to undergo reactivation. 相似文献
56.
Male Wistar rats were subjected to right-unilateral 6-hydroxydopamine (6-OHDA) (2 μg/μl) lesions of the ventral tegmental area (VTA) or the substantia nigra (SN), or were sham-operated, and their ability to acquire
the operant task was studied by means of Y-maze and shuttle-box tasks. Lesions of both the VTA and the SN resulted in an impairment
of conditioned avoidance response and increase of crossing latency tested by means of shuttle-box task, suggesting significant
effects of long-term memory. 6-OHDA significantly decreased spontaneous alternation in Y-maze task, suggesting effects on
spatial memory, especially on short-term memory. In addition, 6-OHDA lesions of the VTA and the SN induced reductions in superoxide
dismutase (SOD), glutathione peroxidase (GPX) activities and malondialdehyde (MDA) levels in the temporal lobe rather than
in the frontal lobe homogenates. Our results provide further support for the toxic effects of 6-OHDA-induced memory impairment
and oxidative stress with relevance for Parkinson’s disease. 相似文献
57.
Cell fate specification and competence by Coco,a maternal BMP,TGFbeta and Wnt inhibitor 总被引:3,自引:0,他引:3
Bell E Muñoz-Sanjuán I Altmann CR Vonica A Brivanlou AH 《Development (Cambridge, England)》2003,130(7):1381-1389
Patterning of the pre-gastrula embryo and subsequent neural induction post-gastrulation are very complex and intricate processes of which little, until recently, has been understood. The earliest decision in neural development, the choice between epidermal or neural fates, is regulated by bone morphogenetic protein (BMP) signaling within the ectoderm. Inhibition of BMP signaling is sufficient for neural induction. Many secreted BMP inhibitors are expressed exclusively within the organizer of the Xenopus gastrula embryo and therefore are predicted to act as bona fide endogenous neural inducers. Other cell-autonomous inhibitors of the BMP pathway are more widely expressed, such as the inhibitory Smads, Smad6 and Smad7. In this report we describe the biological and biochemical characterization of 51-B6, a novel member of Cerberus/Dan family of secreted BMP inhibitors, which we identified in a screen for Smad7-induced genes. This gene is expressed maternally in an animal to vegetal gradient, and its expression levels decline rapidly following gastrulation. In contrast to known BMP inhibitors, 51-B6 is broadly expressed in the ectoderm until the end of gastrulation. The timing, pattern of expression, and activities of this gene makes it unique when compared to other BMP/TGFbeta/Wnt secreted inhibitors which are expressed only zygotically and maintained post-gastrulation. We propose that a function of 51-B6 is to block BMP and TGFbeta signals in the ectoderm in order to regulate cell fate specification and competence prior to the onset of neural induction. In addition, we demonstrate that 51-B6 can act as a neural inducer and induce ectopic head-like structures in neurula staged embryos. Because of this embryological activity, we have renamed this clone Coco, after the Spanish word meaning head. 相似文献
58.
Lao UL Chen A Matsumoto MR Mulchandani A Chen W 《Biotechnology and bioengineering》2007,98(2):349-355
Cadmium contamination of soil is a major concern in the biosphere. Beyond the suite of available physico-chemical treatment methods, green and more efficient technologies are desired to reduce cadmium and other heavy metal contaminants to acceptable levels. Elastin-like polypeptides (ELP) composed of a polyhistidine domain (ELPH12) can be used as an environmentally benign chelating agent for ex situ soil washing. However, ELPH12 is relatively non-selective. A biopolymer with metal-binding domains that have stronger affinity, capacity, and selectivity would have distinct advantages. The aim of this work is to investigate the use of a new generation of ELP biopolymer, ELPEC20, containing synthetic phytochelatin (EC) as the metal-binding domain for ex situ soil washing. ELPEC20 was shown to bind cadmium more effectively and selectively than ELPH12. The binding constant of ELPEC20 is an order of magnitude higher and the binding capacity is fivefold higher than ELPH12. In contrast to ELPH12, no decrease in cadmium binding was observed in the presence of other competing metal ions. The improved selectivity and binding capacity provided by ELPEC20 were directly reflected in the enhanced cadmium extraction efficiency from contaminated soil. In batch washing studies up to 62% of the bound cadmium was removed by ELPEC20 while less than 12% was removed by ELPH12. Cadmium was removed not only from the exchangeable fraction but also the oxidizable fraction. The high-affinity binding sites of ELPEC20 also results in very rapid extraction with complete removal achieved within 1 h, suggesting that ELPEC20 could be used as part of a rapid (short retention time) technology with minimum possibility for the biodegradation of biopolymers. 相似文献
59.
Jihoe Kim Luciana Hannibal Carmen Gherasim Donald W. Jacobsen Ruma Banerjee 《The Journal of biological chemistry》2009,284(48):33418-33424
Pathways for tailoring and processing vitamins into active cofactor forms exist in mammals that are unable to synthesize these cofactors de novo. A prerequisite for intracellular tailoring of alkylcobalamins entering from the circulation is removal of the alkyl group to generate an intermediate that can subsequently be converted into the active cofactor forms. MMACHC, a cytosolic cobalamin trafficking chaperone, has been shown recently to catalyze a reductive decyanation reaction when it encounters cyanocobalamin. In this study, we demonstrate that this versatile protein catalyzes an entirely different chemical reaction with alkylcobalamins using the thiolate of glutathione for nucleophilic displacement to generate cob(I)alamin and the corresponding glutathione thioether. Biologically relevant thiols, e.g. cysteine and homocysteine, cannot substitute for glutathione. The catalytic turnover numbers for the dealkylation of methylcobalamin and 5′-deoxyadenosylcobalamin by MMACHC are 11.7 ± 0.2 and 0.174 ± 0.006 h−1 at 20 °C, respectively. This glutathione transferase activity of MMACHC is reminiscent of the methyltransferase chemistry catalyzed by the vitamin B12-dependent methionine synthase and is impaired in the cblC group of inborn errors of cobalamin disorders. 相似文献
60.
Ciocan-Cȃrtiţă Cristina Alexandra Jurj Ancuţa Raduly Lajos Cojocneanu Roxana Moldovan Alin Pileczki Valentina Pop Laura-Ancuta Budişan Liviuţa Braicu Cornelia Korban Schuyler S. Berindan-Neagoe Ioana 《Molecular and cellular biochemistry》2020,474(1-2):285-294
Molecular and Cellular Biochemistry - Alzheimer’s disease (AD) is a public health issue worldwide. Berberine (Ber) acts as the neuroprotective role in an animal experiment of AD. MicroRNA-188... 相似文献