全文获取类型
收费全文 | 206篇 |
免费 | 26篇 |
出版年
2021年 | 7篇 |
2019年 | 1篇 |
2018年 | 2篇 |
2017年 | 1篇 |
2016年 | 3篇 |
2015年 | 7篇 |
2014年 | 5篇 |
2013年 | 13篇 |
2012年 | 16篇 |
2011年 | 10篇 |
2010年 | 9篇 |
2009年 | 9篇 |
2008年 | 13篇 |
2007年 | 12篇 |
2006年 | 9篇 |
2005年 | 10篇 |
2004年 | 9篇 |
2003年 | 8篇 |
2002年 | 6篇 |
2001年 | 4篇 |
2000年 | 5篇 |
1999年 | 4篇 |
1998年 | 2篇 |
1997年 | 4篇 |
1996年 | 2篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1991年 | 5篇 |
1990年 | 1篇 |
1989年 | 8篇 |
1988年 | 5篇 |
1987年 | 1篇 |
1986年 | 5篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1977年 | 5篇 |
1975年 | 4篇 |
1972年 | 1篇 |
1970年 | 1篇 |
1968年 | 2篇 |
1967年 | 2篇 |
1953年 | 1篇 |
排序方式: 共有232条查询结果,搜索用时 46 毫秒
21.
Ceon?RamonEmail author Hubert?Preissl Pam?Murphy James?D?Wilson Curtis?Lowery Hari?Eswaran 《Biomedical engineering online》2005,4(1):55
Background
Our objective was to quantify and compare the extent of synchronization of the spatial-temporal myometrial activity over the human uterus before and during a contraction using transabdominal magnetomyographic (MMG) recordings. Synchronization can be an important indicator for the quantification of uterine contractions. 相似文献22.
Alexander DE Kaczorowski DJ Jackson-Fisher AJ Lowery DM Zanton SJ Pugh BF 《The Journal of biological chemistry》2004,279(31):32401-32406
The Brf1 subunit of TFIIIB plays an important role in recruiting the TATA-binding protein (TBP) to the up-stream region of genes transcribed by RNA polymerase III. When TBP is not bound to promoters, it sequesters its DNA binding domain through dimerization. Promoter assembly factors therefore might be required to dissociate TBP into productively binding monomers. Here we show that Saccharomyces cerevisiae Brf1 induces TBP dimers to dissociate. The high affinity TBP binding domain of Brf1 is not sufficient to promote TBP dimer dissociation but in addition requires the TFIIB homology domain of Brf1. A model is proposed to explain how two distinct functional domains of Brf1 work in concert to dissociate TBP into monomers. 相似文献
23.
Consisting of a silica core surrounded by a thin gold shell, nanoshells possess an optical tunability that spans the visible to the near infrared (NIR) region, a region where light penetrates tissues deeply. Conjugated with tumor-specific antibodies, NIR-absorbing immunonanoshells can preferentially bind to tumor cells. NIR light then heats the bound nanoshells, thus destroying the targeted cells. Antibodies can be consistently bound to the nanoshells via a bifunctional polyethylene glycol (PEG) linker at a density of approximately 150 antibodies per nanoshell. In vitro studies have confirmed the ability to selectively induce cell death with the photothermal interaction of immunonanoshells and NIR light. Prior to incubation with anti-human epidermal growth factor receptor (HER2) immunonanoshells, HER2-expressing SK-BR-3 breast carcinoma cells were seeded alone or adjacent to human dermal fibroblasts (HDFs). Anti-HER2 immunonanoshells bound to HER2-expressing cells resulted in the death of SK-BR-3 cells after NIR exposure only within the irradiated area, while HDFs remained viable after similar treatment since the immunonanoshells did not bind to these cells at high levels. Control nanoshells, conjugated with nonspecific anti-IgG or PEG, did not bind to either cell type, and cells continued to be viable after treatment with these control nanoshells and NIR irradiation. 相似文献
24.
Wilson PE Nyborg AC Kenealey J Lowery TJ Crawford K King CR Engan AJ Johnson JL Watt GD 《Biophysical chemistry》2006,122(3):184-194
The molybdenum nitrogenase enzyme system, comprised of the MoFe protein and the Fe protein, catalyzes the reduction of atmospheric N(2) to NH(3). Interactions between these two proteins and between Fe protein and nucleotides (MgADP and MgATP) are crucial to catalysis. It is well established that salts are inhibitors of nitrogenase catalysis that target these interactions. However, the implications of salt effects are often overlooked. We have reexamined salt effects in light of a comprehensive framework for nitrogenase interactions to offer an in-depth analysis of the sources of salt inhibition and underlying apparent cooperativity. More importantly, we have identified patterns of salt activation of nitrogenase that correspond to at least two mechanisms. One of these mechanisms is that charge screening of MoFe protein-Fe protein interactions in the nitrogenase complex accelerates the rate of nitrogenase complex dissociation, which is the rate-limiting step of catalysis. This kind of salt activation operates under conditions of high catalytic activity and low salt concentrations that may resemble those found in vivo. While simple kinetic arguments are strong evidence for this kind of salt activation, further confirmation was sought by demonstrating that tight complexes that have previously displayed little or no activity due to the inability of Fe protein to dissociate from the complex are activated by the presence of salt. This occurs for the combination Azotobacter vinelandii MoFe protein with: (a) the L127Delta Fe protein; and (b) Clostridium pasteurianum Fe protein. The curvature of activation vs. salt implies a synergistic salt-protein interaction. 相似文献
25.
Fife MS Gutierrez A Ogilvie EM Stock CJ Samuel JM Thomson W Mack LF Lewis CM Woo P 《Arthritis research & therapy》2006,8(5):R148-5
Juvenile idiopathic arthritis (JIA) is the most common cause of chronic childhood disability and encompasses a number of disease
subgroups. In this study we have focused on systemic JIA (sJIA), which accounts for approximately 11% of UK JIA cases. This
study reports the investigation of three members of the IL10 gene family as candidate susceptibility loci in children with
sJIA. DNA from 473 unaffected controls and 172 patients with sJIA was genotyped for a single nucleotide polymorphism (SNP)
in IL19 and IL20 and two SNPs in IL10. We examined evidence for association of the four SNPs by single marker and haplotype
analysis. Significant differences in allele frequency were observed between cases and controls, for both IL10-1082 (p = 0.031)
and IL20-468 (p = 0.028). Furthermore, examination of the haplotypes of IL10-1082 and IL20-468 revealed greater evidence for
association (global p = 0.0006). This study demonstrates a significant increased prevalence of the low expressing IL10-1082
genotype in patients with sJIA. In addition, we show a separate association with an IL20 polymorphism, and the IL10-1082A/IL20-468T
haplotype. The two marker 'A-T' haplotype confers an odds ratio of 2.24 for sJIA. This positive association suggests an important
role for these cytokines in sJIA pathogenesis. 相似文献
26.
ABSTRACT: BACKGROUND: Binge ethanol in rats after chronic ethanol exposure augments necrosis and steatosis in the liver. In this study, two-dimensional gel electrophoresis proteomic profiles of liver of control, chronic ethanol, control-binge, and chronic ethanol- binge were compared. RESULTS: The proteomic analysis identified changes in protein abundance among the groups. The levels of carbonic anhydrase isoform 3 (CA3) were decreased after chronic ethanol and decreased further after chronic ethanol-binge. Ethanol binge alone in control rats had no effect on this protein suggesting its possible role in increased susceptibility to injury by binge after chonic ethanol treatment. A protein spot, in which both cytosolic isocitrate dehydrogenase (IDH1) and glutamine synthetase (GS) were identified, showed a small decrease after chronic ethanol binge but western blot demonstrated significant decrease only for glutamine synthetase in chronic ethanol treated rats. Level of gluathione S-transferase mu isoform (GSTM1) increased after chronic ethanol but the levels were lower after chronic ethanol-binge compared to chronic ethanol treatment. The protein levels of basic form protein disulfide isomerase associated protein 3 (PDIA3) were significantly decreased and acidic forms were increased after chronic ethanol- binge but not in chronic ethanol treated rats or ethanol binge in control rats. CONCLUSIONS: Given the role of CA3, IDH1 and GST in oxidative stress; PDIA3 in protein quality, apoptosis and DNA repair; and decreased glutamine synthetase as a sensitive marker of pericentral liver injury; this proteome study of chronic ethanol-binge rat model identifies these proteins for the first time as molecular targets with potential role in progression of liver injury by binge ethanol drinking. 相似文献
27.
Taylor EB Lowery E Lilliestråle A Elz A Quinn TP 《Journal of evolutionary biology》2008,21(6):1609-1625
The North Pacific Ocean has been of great significance to understanding biogeography and speciation in temperate faunas, including for two species of char (Salmonidae: Salvelinus) whose evolutionary relationship has been controversial. We examined the morphology and genetics (microsatellite and mitochondrial DNA) of Arctic char (Salvelinus alpinus) and Dolly Varden char (Salvelinus malma) in lake systems in western Alaska, the eastern and western Arctic, and south of the Alaskan Peninsula. Morphologically, each lake system contained two forms: one (Arctic char) largely confined to lake habitats and characterized by greater numbers of pyloric caeca, gill rakers, and shallower bodies, and another (Dolly Varden) predominated in adjacent stream habitats and was characterized by fewer pyloric caeca, gill rakers, and deeper bodies. MtDNA partial (550 bp) d-loop sequences of both taxa were interspersed with each other within a single 'Bering' clade and demographic inferences suggested historical gene flow from Dolly Varden to Arctic char had occurred. By contrast, the taxa were strongly differentiated in sympatry across nine microsatellite loci in both lakes. Our data show that the two taxa are highly genetically distinct in sympatry, supporting their status as valid biological species, despite occasional hybridization. The interaction between these species highlights the importance of the North Pacific, and Beringia in particular, as an evolutionary wellspring of biodiversity. 相似文献
28.
C.J. Lowery J.E. Moore B.C. Millar K.A.J. McCorry J. Xu P.J. Rooney & J.S.G. Dooley 《Journal of applied microbiology》2001,91(5):774-779
AIMS: To investigate the incidence and genotype of Cryptosporidium parvum oocysts in drinking water sources in Northern Ireland for the period 1996-1999, and to compare conventional and molecular methods of detection. METHODS AND RESULTS: Four hundred and seventy-four waters were investigated by conventional methods, namely immuno-fluorescent antibody detection (IFA; 380) and immuno-magnetic separation-IFA (IMS-IFA; 94), of which 14/474 (3%) were positive. Two hundred and fourteen samples (214/474) were also investigated by PCR techniques, targeting both the 18S rRNA and TRAP-C2 genes, of which 11/214 (5.1%) were positive. These 11 samples were classified as genotype II following sequence analysis of the TRAP-C2 amplicon. CONCLUSIONS: This study demonstrated the low incidence of oocysts of C. parvum in water sources in Northern Ireland. SIGNIFICANCE AND IMPACT OF THE STUDY: Such molecular-based techniques offer a number of advantages over conventional detection methodologies, namely greater sensitivity and specificity as well as the ability to provide accurate genotyping data rapidly, which may be valuable in directing operational management in potential outbreak situations. 相似文献
29.
Carla Hajj James Russell Charles P Hart Karyn A Goodman Maeve A Lowery Adriana Haimovitz-Friedman Joseph O. Deasy John L. Humm 《Translational oncology》2017,10(5):760-765
This study was designed to investigate the effect of single-dose radiation therapy (RT) in combination with evofosfamide (TH-302), a hypoxia-activated prodrug, in a pre-clinical model of pancreatic cancer. AsPC1 tumors were implanted orthotopically in the pancreas of nude mice. Tumors were treated with 15 Gy of RT, using a 1 cm diameter field, and delivered as a continuous arc. Image-guidance to center the field on the tumor was based on CT imaging with intraperitoneal contrast. Evofosfamide (100 mg/kg, i.p.) was administered 3 hours before RT. Tumor volumes were measured using ultrasound, and regrowth curves were plotted. Tumor hypoxia and cell proliferation were measured using pimonidazole and the thymidine analog EdU, respectively. In vitro clonogenic assays were performed. Tumors were shown to contain substantial areas of hypoxia, as calculated by percent pimonidazole staining. Evofosfamide was active in these tumors, as demonstrated by a significant reduction in uptake of the thymidine analog EdU. This effect was visible in oxygenated tissue, consistent with the previously reported bystander effects of evofosfamide. RT produced significant regrowth delay, as did evofosfamide. The combination of both agents produced a growth delay that was at least equal to the sum of the two treatments given separately. The improvement in tumor response when evofosfamide is combined with RT supports the hypothesis that hypoxia is a cause of radioresistance in high dose RT for pancreatic cancer. Assessing the efficacy and safety of stereotactic radiation treatment and evofosfamide is warranted in patients with locally advanced pancreatic cancer. 相似文献
30.
Identification of suitable endogenous control genes for microRNA gene expression analysis in human breast cancer 总被引:2,自引:0,他引:2
Pamela A Davoren Roisin E McNeill Aoife J Lowery Michael J Kerin Nicola Miller 《BMC molecular biology》2008,9(1):76
The discovery of microRNAs (miRNAs) added an extra level of intricacy to the already complex system regulating gene expression.
These single-stranded RNA molecules, 18–25 nucleotides in length, negatively regulate gene expression through translational
inhibition or mRNA cleavage. The discovery that aberrant expression of specific miRNAs contributes to human disease has fueled
much interest in profiling the expression of these molecules. Real-time quantitative PCR (RQ-PCR) is a sensitive and reproducible
gene expression quantitation technique which is now being used to profile miRNA expression in cells and tissues. To correct
for systematic variables such as amount of starting template, RNA quality and enzymatic efficiencies, RQ-PCR data is commonly
normalised to an endogenous control (EC) gene, which ideally, is stably-expressed across the test sample set. A universal
endogenous control suitable for every tissue type, treatment and disease stage has not been identified and is unlikely to
exist, so, to avoid introducing further error in the quantification of expression data it is necessary that candidate ECs
be validated in the samples of interest. While ECs have been validated for quantification of mRNA expression in various experimental
settings, to date there is no report of the validation of miRNA ECs for expression profiling in breast tissue. In this study,
the expression of five miRNA genes (let-7a, miR-10b, miR-16, miR-21 and miR-26b) and three small nucleolar RNA genes (RNU19, RNU48 and Z30) was examined across malignant, benign and normal breast tissues to determine the most appropriate normalisation strategy.
This is the first study to identify reliable ECs for analysis of miRNA by RQ-PCR in human breast tissue. 相似文献