全文获取类型
收费全文 | 60篇 |
免费 | 13篇 |
国内免费 | 1篇 |
出版年
2017年 | 1篇 |
2016年 | 2篇 |
2015年 | 1篇 |
2014年 | 4篇 |
2013年 | 5篇 |
2012年 | 1篇 |
2011年 | 3篇 |
2010年 | 2篇 |
2009年 | 3篇 |
2008年 | 2篇 |
2007年 | 2篇 |
2006年 | 4篇 |
2005年 | 3篇 |
2004年 | 1篇 |
2003年 | 1篇 |
2002年 | 2篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 3篇 |
1997年 | 3篇 |
1996年 | 3篇 |
1994年 | 1篇 |
1993年 | 3篇 |
1992年 | 1篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1981年 | 3篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有74条查询结果,搜索用时 15 毫秒
51.
52.
E D Foehr S Raffioni J Murray-Rust R A Bradshaw 《The Journal of biological chemistry》2001,276(40):37529-37536
To assess the contribution of the intracellular domain tyrosine residues to the signaling capacity of fibroblast growth factor receptor 1 (FGFR1), stably transfected chimeras bearing the ectodomain of the platelet-derived growth factor receptor (PDGFR) and the endodomain of FGFR1 were systematically altered by a tyrosine to phenylalanine bloc and individual conversions. The 15 tyrosine residues of the endodomain of this construct (PFR1) were divided into four linear segments (labeled A, B, C, and D) that contained 4, 4, 2, and 5 tyrosine residues, respectively. When stimulated by platelet-derived growth factor, derivatives in which the A, B, or A + B blocs of tyrosines were mutated were about two-thirds as active as the unmodified chimera at 48 h but achieved full activity by 96 h in a neurite outgrowth assay in transfected PC12 cells. Elimination of only the two activation loop tyrosines (C bloc) also inactivated the receptor. All derivatives in which 4 (or 5) of the D bloc tyrosines were mutated were inactive in producing differentiation but showed low levels of kinase activity in in vitro assays. Derivatives in which 1, 2, or 3 tyrosines of the D bloc in different combinations were systematically changed demonstrated that 2 residues (Tyr(677) and Tyr(701), using hFGFR1 numbering) were essential for bioactivity, but the remaining 3 residues, including Tyr(766), the previously identified site for phospholipase C gamma (PLC gamma) activation, were not. Differentiation activity was paralleled by the activation (phosphorylation) of FRS2, SOS, and ERK1/2. PLC gamma activity was dependent on the presence of Tyr(766) but also required Tyr(677) and/or Tyr(701). Although fully active chimeras did not require PLC gamma, the responses of chimeras showing reduced activation of FRS2 were significantly enhanced by this activity. These results establish that PFR1 does not utilize any tyrosine residues, phosphorylated or not, to activate FRS2. However, it does require Tyr(677) and/or Tyr(701), which may function to stabilize the active conformation directly or indirectly. 相似文献
53.
M Ozkan SG Desai Y Zhang DM Stevenson J Beane EA White ML Guerinot LR Lynd 《Journal of industrial microbiology & biotechnology》2001,27(5):275-280
Characteristics of 13 newly isolated thermophilic, anaerobic, and cellulolytic strains were compared with previously described
strains of Clostridium thermocellum: ATCC 27405 and JW20 (ATCC 31549). Colony morphology, antibiotic sensitivity, fermentation end-products, and cellulose degradation
were documented. All 13 strains were sensitive to erythromycin (5 μg/ml) and chloramphenicol (25 μg/ml), and all strains but
one were sensitive to kanamycin (20 μg/ml). Polymerase chain reaction (PCR) amplification using primers based on gene sequences
from C. thermocellum ATCC 27405 was successful for all 13 strains in the case of the hydrogenase gene and 11 strains in the case of phosphotransacetylase/acetate
kinase genes. Ten strains amplified a product of the expected size with primers developed to be specific for C. thermocellum 16SrRNA primers. Two of the 13 strains did not amplify any product with the PCR primers designed for the phosphotransacetylase/acetate
kinase and 16SrRNA primers. A MboI-like GATC- recognizing restriction activity was present in all of the five strains examined. The results of this study have
several positive implications with respect to future development of a transformation system for cellulolytic thermophiles.
Journal of Industrial Microbiology & Biotechnology (2001) 27, 275–280.
Received 12 September 2000/ Accepted in revised form 20 November 2000 相似文献
54.
We present BioGraph, a data integration and data mining platform for the exploration and discovery of biomedical information.
The platform offers prioritizations of putative disease genes, supported by functional hypotheses. We show that BioGraph can
retrospectively confirm recently discovered disease genes and identify potential susceptibility genes, outperforming existing
technologies, without requiring prior domain knowledge. Additionally, BioGraph allows for generic biomedical applications
beyond gene discovery. BioGraph is accessible at . 相似文献
55.
D Bagga N Singh S Modi P Kumar D Bhattacharya ML Garg S Khushu 《Journal of biosciences》2013,38(5):905-915
Neuropsychological studies have shown that alcohol dependence is associated with neurocognitive deficits in tasks requiring memory, perceptual motor skills, abstraction and problem solving, whereas language skills are relatively spared in alcoholics despite structural abnormalities in the language-related brain regions. To investigate the preserved mechanisms of language processing in alcohol-dependents, functional brain imaging was undertaken in healthy controls (n=18) and alcohol-dependents (n=16) while completing a lexical semantic judgment task in a 3 T MR scanner. Behavioural data indicated that alcohol-dependents took more time than controls for performing the task but there was no significant difference in their response accuracy. fMRI data analysis revealed that while performing the task, the alcoholics showed enhanced activations in left supramarginal gyrus, precuneus bilaterally, left angular gyrus, and left middle temporal gyrus as compared to control subjects. The extensive activations observed in alcoholics as compared to controls suggest that alcoholics recruit additional brain areas to meet the behavioural demands for equivalent task performance. The results are consistent with previous fMRI studies suggesting compensatory mechanisms for the execution of task for showing an equivalent performance or decreased neural efficiency of relevant brain networks. However, on direct comparison of the two groups, the results did not survive correction for multiple comparisons; therefore, the present findings need further exploration. 相似文献
56.
In response to hypoxia, tissues have to implement numerous mechanisms to enhance oxygen delivery, including the activation of angiogenesis. This work investigates the angiogenic response of the hypoxic caudate putamen after several recovery times. Adult Wistar rats were submitted to acute hypoxia and analysed after 0 h, 24 h and 5 days of reoxygenation. Expression of hypoxia-inducible factor-1 alfa (HIF-1α) and angiogenesis-related genes including vascular endothelial growth factor (VEGF), adrenomedullin (ADM) and transforming growth factor-beta 1 (TGF-β1) was determined by both RT-PCR and ELISA. For vessel labelling, lectin location and expression were analysed using histochemical and image processing techniques (fractal dimension). Expression of Hif-1α, Vegf, Adm and Tgf-β1 mRNA rose immediately after hypoxia and this increase persisted in some cases after 5 days post-hypoxia. While VEGF and TGF-β1 protein levels increased parallel to mRNA expression, ADM remained unaltered. The quantification of the striatal vessel network showed a significant augmentation at 24 h of reoxygenation. These results reveal that not only short-term hypoxia, but also the subsequent reoxygenation period, up-regulate the angiogenic pathway in the rat caudate putamen as a neuroprotective mechanism to hypoxia that seeks to maintain a proper blood supply to the hypoxic tissue, thereby minimizing the adverse effects of oxygen deprivation. 相似文献
57.
Loss of meiosis in Aspergillus 总被引:2,自引:0,他引:2
If strictly mitotic asexual fungi lack recombination, the conventional view
predicts that they are recent derivatives from older meiotic lineages. We
tested this by inferring phylogenetic relationships among closely related
meiotic and strictly mitotic taxa with Aspergillus conidial (mitotic)
states. Phylogenies were constructed by using DNA sequences from the
mitochondrial small ribosomal subunit, the nuclear ribosomal internal
transcribed spacers, and the nuclear 5.8S ribosomal gene. Over 920 bp of
sequence was analyzed for each taxon. Phylogenetic analysis of both the
mitochondrial and nuclear data sets showed at least four clades that
possess both meiotic and strictly mitotic taxa. These results support the
hypothesis that strictly mitotic lineages arise frequently from more
ancient meiotic lineages with Aspergillus conidial states. Many of the
strictly mitotic species examined retained characters that may be vestiges
of a meiotic state, including the production of sclerotia, sclerotium-like
structures, and hulle cells.
相似文献
58.
59.
Umansky SR Shapiro JP Cuenco GM Foehr MW Bathurst IC Tomei LD 《Cell death and differentiation》1997,4(7):608-616
Apoptosis, or programmed cell death, is an active metabolic response to physiological signals or exposure to cytotoxic agents. Recent evidence has shown that the cell death response can be modified by agents presumed to be unrelated to the initial signal, but capable of interfering with the molecular mechanisms of the apoptotic pathway progression. Here we show the results of investigations on the use of a phospholipid-based pharmaceutical preparation for suppression of myocardial damage. First, we show that serum or serum/glucose deprivation, in vitro ischemia with subsequent simulated reperfusion, inhibition of protein synthesis, and treatment with ceramide, staurosporine, adriamycin, cis-platinum and menadione induce apoptotic death in a primary culture of rat neonatal cardiomyocytes. Then we demonstrate that a mixture of specific phospholipids, which has been originally purified from soy flour on the basis of its anti-apoptotic activity, prevents cardiomyocyte death induced by serum or serum/glucose deprivation, by ischemia with subsequent simulated reperfusion, and by ceramide, but not by other cytotoxic treatments. This suggests that ceramide, a lipid secondary messenger which triggers apoptosis induced by some cytotoxic agents, may be involved in the process of signaling ischemia/reperfusion induced apoptotic death of cardiomyocytes. These results further demonstrate that an active pharmaceutical preparation for the suppression of cardiomyocyte death can be formulated based upon a novel strategy of apoptosis modification. 相似文献
60.
The tissue and developmental specificities of the three Drosophila isoactins, originally identified in primary myogenic cultures and in the permanent Schneider L-2 cell line, have been investigated. Of these three isoactins (I, II, and III), actins I and II are stable and actin III is unstable. Two-dimensional polyacrylamide gel electrophoretic analyses of total cellular extracts after 1-h [(35)S]methionine pulses were performed on a large variety of embryonic, larval, and adult muscle and nonmuscle tissues. The results suggest that isoactins II and III are generalized cellular actins found in all drosophila cell types. Actin I, on the other hand, is muscle-associated and is found exclusively in supercontractile muscle (such as larval body wall and larval and adult viscera) including primary myogenic cell cultures. Although actin I synthesis is not detectable during very early embryogenesis, it is detectable by 25 h and actin I is a major stable actin in all larval muscle tissues. Actin I is synthesized in reduced amounts relative to the other actins in late third instar larvae but is again a major product of actin synthesis in the adult abdomen. A stable actin species with the same pI as actin III has been identified in the adult thorax and appears to be unique to flight muscle tissue. This new stable form of thoracic actin may be the result of a stabilization of the actin III found in other tissues or may be an entirely separate gene product. 相似文献