全文获取类型
收费全文 | 188篇 |
免费 | 21篇 |
出版年
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 4篇 |
2020年 | 1篇 |
2018年 | 1篇 |
2016年 | 4篇 |
2015年 | 5篇 |
2014年 | 12篇 |
2013年 | 8篇 |
2012年 | 13篇 |
2011年 | 16篇 |
2010年 | 10篇 |
2009年 | 5篇 |
2008年 | 19篇 |
2007年 | 7篇 |
2006年 | 17篇 |
2005年 | 16篇 |
2004年 | 10篇 |
2003年 | 13篇 |
2002年 | 7篇 |
2001年 | 2篇 |
2000年 | 3篇 |
1999年 | 3篇 |
1998年 | 1篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1990年 | 1篇 |
1988年 | 1篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1966年 | 2篇 |
1965年 | 3篇 |
1962年 | 1篇 |
1961年 | 1篇 |
1954年 | 1篇 |
排序方式: 共有209条查询结果,搜索用时 31 毫秒
11.
12.
RNase P: role of distinct protein cofactors in tRNA substrate recognition and RNA-based catalysis 总被引:2,自引:1,他引:1
下载免费PDF全文
![点击此处可从《Nucleic acids research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The Escherichia coli ribonuclease P (RNase P) has a protein component, termed C5, which acts as a cofactor for the catalytic M1 RNA subunit that processes the 5′ leader sequence of precursor tRNA. Rpp29, a conserved protein subunit of human RNase P, can substitute for C5 protein in reconstitution assays of M1 RNA activity. To better understand the role of the former protein, we compare the mode of action of Rpp29 to that of the C5 protein in activation of M1 RNA. Enzyme kinetic analyses reveal that complexes of M1 RNA–Rpp29 and M1 RNA–C5 exhibit comparable binding affinities to precursor tRNA but different catalytic efficiencies. High concentrations of substrate impede the activity of the former complex. Rpp29 itself exhibits high affinity in substrate binding, which seems to reduce the catalytic efficiency of the reconstituted ribonucleoprotein. Rpp29 has a conserved C-terminal domain with an Sm-like fold that mediates interaction with M1 RNA and precursor tRNA and can activate M1 RNA. The results suggest that distinct protein folds in two unrelated protein cofactors can facilitate transition from RNA- to ribonucleoprotein-based catalysis by RNase P. 相似文献
13.
Kantor R Katzenstein DA Efron B Carvalho AP Wynhoven B Cane P Clarke J Sirivichayakul S Soares MA Snoeck J Pillay C Rudich H Rodrigues R Holguin A Ariyoshi K Bouzas MB Cahn P Sugiura W Soriano V Brigido LF Grossman Z Morris L Vandamme AM Tanuri A Phanuphak P Weber JN Pillay D Harrigan PR Camacho R Schapiro JM Shafer RW 《PLoS medicine》2005,2(4):e112
BackgroundThe genetic differences among HIV-1 subtypes may be critical to clinical management and drug resistance surveillance as antiretroviral treatment is expanded to regions of the world where diverse non-subtype-B viruses predominate.ConclusionGlobal surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations. 相似文献
14.
Schwimmer C Lefebvre-Legendre L Rak M Devin A Slonimski PP di Rago JP Rigoulet M 《The Journal of biological chemistry》2005,280(35):30751-30759
In a previous study we have identified Fmc1p, a mitochondrial protein involved in the assembly/stability of the yeast F0F1-ATP synthase at elevated temperatures. The deltafmc1 mutant was shown to exhibit a severe phenotype of very slow growth on respiratory substrates at 37 degrees C. We have isolated ODC1 as a multicopy suppressor of the fmc1 deletion restoring a good respiratory growth. Odc1p expression level was estimated to be at least 10 times higher in mitochondria isolated from the deltafmc1/ODC1 transformant as compared with wild type mitochondria. Interestingly, ODC1 encodes an oxodicarboxylate carrier, which transports alpha-ketoglutarate and alpha-ketoadipate or any other transported tricarboxylic acid cycle intermediate in a counter-exchange through the inner mitochondrial membrane. We show that the suppression of the respiratory-growth-deficient fmc1 by the overexpressed Odc1p was not due to a restored stable ATP synthase. Instead, the rescuing mechanism involves an increase in the flux of tricarboxylic acid cycle intermediate from the cytosol into the mitochondria, leading to an increase in the alpha-ketoglutarate oxidative decarboxylation, resulting in an increase in mitochondrial substrate-level-dependent ATP synthesis. This mechanism of metabolic bypass of a defective ATP synthase unravels the physiological importance of intramitochondrial substrate-level phosphorylations. This unexpected result might be of interest for the development of therapeutic solutions in pathologies associated with defects in the oxidative phosphorylation system. 相似文献
15.
Role of GPR40 in fatty acid action on the beta cell line INS-1E 总被引:7,自引:0,他引:7
Shapiro H Shachar S Sekler I Hershfinkel M Walker MD 《Biochemical and biophysical research communications》2005,335(1):97-104
GPR40 is a G protein-coupled receptor expressed preferentially in beta cells, that has been implicated in mediating free fatty acid-stimulated insulin release. GPR40 RNAi impaired the ability of palmitic acid (PA) to increase both insulin secretion and intracellular calcium ([Ca2+]i). The PA-dependent [Ca2+]i increase was attenuated by inhibitors of Galphaq, PLC, and SERCA. Thus GPR40 activates the Galphaq pathway, leading to release of Ca2+ from the ER. Yet the GPR40-dependent [Ca2+]i rise was dependent on extracellular Ca2+ and elevated glucose, and was blocked by inhibition of L-type calcium channels (LTCC) or opening of the K(ATP) channel; this suggests that GPR40 promotes Ca2+ influx through up-regulation of LTCC pre-activated by glucose and membrane depolarization. Taken together, the data indicate that GPR40 mediates the increase in [Ca2+]i and insulin secretion through the Galphaq-PLC pathway, resulting in release of Ca2+ from the ER and leading to up-regulation of Ca2+ influx via LTCC. 相似文献
16.
Khateeb S Flusser H Ofir R Shelef I Narkis G Vardi G Shorer Z Levy R Galil A Elbedour K Birk OS 《American journal of human genetics》2006,79(5):942-948
Infantile neuroaxonal dystrophy (INAD) is an autosomal recessive progressive neurodegenerative disease that presents within the first 2 years of life and culminates in death by age 10 years. Affected individuals from two unrelated Bedouin Israeli kindreds were studied. Brain imaging demonstrated diffuse cerebellar atrophy and abnormal iron deposition in the medial and lateral globus pallidum. Progressive white-matter disease and reduction of the N-acetyl aspartate : chromium ratio were evident on magnetic resonance spectroscopy, suggesting loss of myelination. The clinical and radiological diagnosis of INAD was verified by sural nerve biopsy. The disease gene was mapped to a 1.17-Mb locus on chromosome 22q13.1 (LOD score 4.7 at recombination fraction 0 for SNP rs139897), and an underlying mutation common to both affected families was identified in PLA2G6, the gene encoding phospholipase A2 group VI (cytosolic, calcium-independent). These findings highlight a role of phospholipase in neurodegenerative disorders. 相似文献
17.
Blomqvist ME Reynolds C Katzov H Feuk L Andreasen N Bogdanovic N Blennow K Brookes AJ Prince JA 《Human genetics》2006,119(1-2):29-37
Most genetic sequence variants that contribute to variability in complex human traits will have small effects that are not
readily detectable with population samples typically used in genetic association studies. A potentially valuable tool in the
gene discovery process is meta-analysis of the accumulated published data, but in order to be valid these require a sample
of studies representative of the true genetic effect and thus hypothetically should include some positive and an abundance
of negative reports. A survey of the literature on association studies for Alzheimer disease (AD) from January 2004–April
2005, identified 138 studies, 86 of which reported positive findings other than for apolipoprotein E (APOE), strongly indicative of publication bias. We report here an analysis of 62 genetic markers, tested for association with
AD risk as well as for possible effects upon quantitative indices of AD severity (mini-mental state examination scores, age-at-onset,
and cerebrospinal fluid (CSF) β-amyloid (Aβ) and CSF tau proteins). Within this set, only modest signals were present that,
with the exception of APOE are easily lost when corrections for multiple hypotheses are applied. In isolation, results are thus broadly negative. Genes
studied encompass both novel candidates as well as several recently claimed to be associated with AD (e.g. urokinase plasminogen
activator (PLAU) and acetyl-coenzyme A acetyltransferase 1 (ACAT1)). By reporting these data we hope to encourage the publication of gene compendia to guide further studies and aid future
meta-analyses aimed at resolving the involvement of genes in complex human traits. 相似文献
18.
Understanding the ways environmental signals, regulate reproduction and reproductive behavior of desert adapted rodents is a major gap in our knowledge. In this study, we assessed the roles of photoperiod and diet salinity, as signals for reproduction. We challenged desert adapted common spiny mice, Acomys cahirinus, males and females with osmotic stress, by gradually increasing salinity in their water source - from 0.9% to 5% NaCl under short and long days (SD and LD, respectively). Photoperiodicity affected testosterone levels, as under LD-acclimation, levels were significantly (p<0.05) higher than under SD-acclimation. Salinity treatment (ST) significantly reduced SD-acclimated male body mass (W(b)) and testis mass (p<0.005; normalized to W(b)). ST-LD-females significantly (p<0.005) decreased progesterone levels and the numbers of estrous cycles. A reduction in white adipose tissue (WAT) to an undetectable level was noted in ST-mice of both sexes under both photoperiod regimes. Receptors for vasopressin (VP) and aldosterone were revealed on testes of all male groups and on WAT in control groups. Our results suggest that photoperiod serves as an initial signal while water availability, expressed by increased salinity in the water source, is an ultimate cue for regulation of reproduction, in both sexes of desert-adapted A. cahirinus. We assume that environmental changes also affect behavior, as water seeking behavior by selecting food items, or locomotor activity may change in extreme environment, and thus indirectly affect reproduction and reproductive behavior. The existence of VP and aldosterone receptors in the gonads and WAT suggests the involvement of osmoregulatory hormones in reproductive control of desert adapted rodents. 相似文献
19.
Anália Louren?o Michael Conover Andrew Wong Azadeh Nematzadeh Fengxia Pan Hagit Shatkay Luis M Rocha 《BMC bioinformatics》2012,13(1):1-3
Correction to A. Louren?o, M. Conover, A. Wong, A. Nematzadeh, F. Pan, H. Shatkay, and L.M. Rocha."A Linear Classifier Based on Entity Recognition Tools and a Statistical Approach to Method Extraction in the Protein-Protein Interaction Literature". BMC Bioinformatics 2011, 12(Suppl 8):S12. doi:http://10.1186/1471-2105-12-S8-S12. 相似文献
20.
H5-type influenza virus hemagglutinin is functionally recognized by the natural killer-activating receptor NKp44 总被引:1,自引:0,他引:1
Ho JW Hershkovitz O Peiris M Zilka A Bar-Ilan A Nal B Chu K Kudelko M Kam YW Achdout H Mandelboim M Altmeyer R Mandelboim O Bruzzone R Porgador A 《Journal of virology》2008,82(4):2028-2032
Antiviral immune defenses involve natural killer (NK) cells. We previously showed that the NK-activating receptor NKp44 is involved in the functional recognition of H1-type influenza virus strains by NK cells. In the present study, we investigated the interaction of NKp44 and the hemagglutinin of a primary influenza virus H5N1 isolate. Here we show that recombinant NKp44 recognizes H5-expressing cells and specifically interacts with soluble H5 hemagglutinin. H5-pseudotyped lentiviral particles bind to NK cells expressing NKp44. Following interaction with target cells expressing H5, pseudotyped lentiviral particles, or membrane-associated H5, NK cells show NKp44-mediated induced activity. These findings indicate that NKp44-H5 interactions induce functional NK activation. 相似文献