全文获取类型
收费全文 | 373篇 |
免费 | 53篇 |
专业分类
426篇 |
出版年
2023年 | 5篇 |
2022年 | 4篇 |
2017年 | 2篇 |
2016年 | 2篇 |
2015年 | 11篇 |
2014年 | 9篇 |
2013年 | 12篇 |
2012年 | 22篇 |
2011年 | 22篇 |
2010年 | 9篇 |
2009年 | 10篇 |
2008年 | 17篇 |
2007年 | 19篇 |
2006年 | 9篇 |
2005年 | 17篇 |
2004年 | 12篇 |
2003年 | 19篇 |
2002年 | 17篇 |
2001年 | 21篇 |
2000年 | 18篇 |
1999年 | 12篇 |
1998年 | 5篇 |
1997年 | 12篇 |
1996年 | 2篇 |
1995年 | 9篇 |
1994年 | 6篇 |
1992年 | 8篇 |
1991年 | 8篇 |
1990年 | 10篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1987年 | 6篇 |
1986年 | 5篇 |
1985年 | 6篇 |
1984年 | 3篇 |
1983年 | 7篇 |
1981年 | 2篇 |
1980年 | 4篇 |
1979年 | 8篇 |
1978年 | 2篇 |
1977年 | 4篇 |
1974年 | 5篇 |
1973年 | 2篇 |
1970年 | 2篇 |
1968年 | 2篇 |
1967年 | 2篇 |
1966年 | 2篇 |
1963年 | 3篇 |
1900年 | 2篇 |
1888年 | 2篇 |
排序方式: 共有426条查询结果,搜索用时 15 毫秒
91.
Cecilie Jonsgar Sandberg Gabriel Altschuler Jieun Jeong Kirsten Kierulf Strømme Biljana Stangeland Wayne Murrell Unn-Hilde Grasmo-Wendler Ola Myklebost Eirik Helseth Einar Osland Vik-Mo Winston Hide Iver A. Langmoen 《Experimental cell research》2013
Glioblastoma is the most common brain tumor. Median survival in unselected patients is <10 months. The tumor harbors stem-like cells that self-renew and propagate upon serial transplantation in mice, although the clinical relevance of these cells has not been well documented. We have performed the first genome-wide analysis that directly relates the gene expression profile of nine enriched populations of glioblastoma stem cells (GSCs) to five identically isolated and cultivated populations of stem cells from the normal adult human brain. Although the two cell types share common stem- and lineage-related markers, GSCs show a more heterogeneous gene expression. We identified a number of pathways that are dysregulated in GSCs. A subset of these pathways has previously been identified in leukemic stem cells, suggesting that cancer stem cells of different origin may have common features. Genes upregulated in GSCs were also highly expressed in embryonic and induced pluripotent stem cells. We found that canonical Wnt-signaling plays an important role in GSCs, but not in adult human neural stem cells. As well we identified a 30-gene signature highly overexpressed in GSCs. The expression of these signature genes correlates with clinical outcome and demonstrates the clinical relevance of GSCs. 相似文献
92.
93.
William Murrell 《BMJ (Clinical research ed.)》1900,2(2086):1823-1824
94.
Characterization of a noncyst-forming isolate of Trichinella from a wild boar in Yugoslavia. 总被引:1,自引:0,他引:1
A Marinculic H R Gamble D S Zarlenga D Rapic Z Kozaric V Imamovic K D Murrell 《The Journal of parasitology》1991,77(2):224-230
An isolate of Trichinella obtained from a wild boar in Yugoslavia did not form cysts in the musculature of its natural host. Subsequent inoculation into experimental hosts demonstrated that some larvae became encysted only after extended time periods, whereas others remained unencapsulated. Histological staining of larvae in the musculature demonstrated no deposition of collagen typically seen for Trichinella spiralis spiralis, Trichinella spiralis nativa, or Trichinella spiralis nelsoni. The Yugoslavian isolate, given the name of Zagreb isolate after the University where it was first studied, had low infectivity for pigs and mice. Isozyme analysis demonstrated greater homology with T. s. nelsoni than with other subspecies of Trichinella. Restriction fragment length polymorphisms and dot blot analyses further demonstrated the distinctive nature of this isolate. These results suggest that lack of cyst formation might be characteristic of isolates other than those designated Trichinella pseudospiralis and that this character might be important in the classification of Trichinella. 相似文献
95.
Chakkiath Paul Antony Deepak Kumaresan Sindy Hunger Harold L Drake J Colin Murrell Yogesh S Shouche 《The ISME journal》2013,7(3):468-476
Soda lakes are saline and alkaline ecosystems that are believed to have existed throughout the geological record of Earth. They are widely distributed across the globe, but are highly abundant in terrestrial biomes such as deserts and steppes and in geologically interesting regions such as the East African Rift valley. The unusual geochemistry of these lakes supports the growth of an impressive array of microorganisms that are of ecological and economic importance. Haloalkaliphilic Bacteria and Archaea belonging to all major trophic groups have been described from many soda lakes, including lakes with exceptionally high levels of heavy metals. Lonar Lake is a soda lake that is centered at an unusual meteorite impact structure in the Deccan basalts in India and its key physicochemical and microbiological characteristics are highlighted in this article. The occurrence of diverse functional groups of microbes, such as methanogens, methanotrophs, phototrophs, denitrifiers, sulfur oxidizers, sulfate reducers and syntrophs in soda lakes, suggests that these habitats harbor complex microbial food webs that (a) interconnect various biological cycles via redox coupling and (b) impact on the production and consumption of greenhouse gases. Soda lake microorganisms harbor several biotechnologically relevant enzymes and biomolecules (for example, cellulases, amylases, ectoine) and there is the need to augment bioprospecting efforts in soda lake environments with new integrated approaches. Importantly, some saline and alkaline lake ecosystems around the world need to be protected from anthropogenic pressures that threaten their long-term existence. 相似文献
96.
Root exudates modify bacterial diversity of phenanthrene degraders in PAH-polluted soil but not phenanthrene degradation rates 总被引:2,自引:0,他引:2
Cébron A Louvel B Faure P France-Lanord C Chen Y Murrell JC Leyval C 《Environmental microbiology》2011,13(3):722-736
To determine whether the diversity of phenanthrene‐degrading bacteria in an aged polycyclic aromatic hydrocarbon (PAH) contaminated soil is affected by the addition of plant root exudates, DNA stable isotope probing (SIP) was used. Microcosms of soil with and without addition of ryegrass exudates and with 13C‐labelled phenanthrene (PHE) were monitored over 12 days. PHE degradation was slightly delayed in the presence of added exudate after 4 days of incubation. After 12 days, 68% of added PHE disappeared both with and without exudate. Carbon balance using isotopic analyses indicated that a part of the 13C‐PHE was not totally mineralized as 13CO2 but unidentified 13C‐compounds (i.e. 13C‐PHE or 13C‐labelled metabolites) were trapped into the soil matrix. Temporal thermal gradient gel electrophoresis (TTGE) analyses of 16S rRNA genes were performed on recovered 13C‐enriched DNA fractions. 16S rRNA gene banding showed the impact of root exudates on diversity of PHE‐degrading bacteria. With PHE as a fresh sole carbon source, Pseudoxanthomonas sp. and Microbacterium sp. were the major PHE degraders, while in the presence of exudates, Pseudomonas sp. and Arthrobacter sp. were favoured. These two different PHE‐degrading bacterial populations were also distinguished through detection of PAH‐ring hydroxylating dioxygenase (PAH‐RHDα) genes by real‐time PCR. Root exudates favoured the development of a higher diversity of bacteria and increased the abundance of bacteria containing known PAH‐RHDα genes. 相似文献
97.
Murrell A Ito Y Verde G Huddleston J Woodfine K Silengo MC Spreafico F Perotti D De Crescenzo A Sparago A Cerrato F Riccio A 《PloS one》2008,3(3):e1849
Background
Differentially methylated regions (DMRs) are associated with many imprinted genes. In mice methylation at a DMR upstream of the H19 gene known as the Imprint Control region (IC1) is acquired in the male germline and influences the methylation status of DMRs 100 kb away in the adjacent Insulin-like growth factor 2 (Igf2) gene through long-range interactions. In humans, germline-derived or post-zygotically acquired imprinting defects at IC1 are associated with aberrant activation or repression of IGF2, resulting in the congenital growth disorders Beckwith-Wiedemann (BWS) and Silver-Russell (SRS) syndromes, respectively. In Wilms tumour and colorectal cancer, biallelic expression of IGF2 has been observed in association with loss of methylation at a DMR in IGF2. This DMR, known as DMR0, has been shown to be methylated on the silent maternal IGF2 allele presumably with a role in repression. The effect of IGF2 DMR0 methylation changes in the aetiology of BWS or SRS is unknown.Methodology/Principal Findings
We analysed the methylation status of the DMR0 in BWS, SRS and Wilms tumour patients by conventional bisulphite sequencing and pyrosequencing. We show here that, contrary to previous reports, the IGF2 DMR0 is actually methylated on the active paternal allele in peripheral blood and kidney. This is similar to the IC1 methylation status and is inconsistent with the proposed silencing function of the maternal IGF2 allele. Beckwith-Wiedemann and Silver-Russell patients with IC1 methylation defects have similar methylation defects at the IGF2 DMR0, consistent with IC1 regulating methylation at IGF2 in cis. In Wilms tumour, however, methylation profiles of IC1 and IGF2 DMR0 are indicative of methylation changes occurring on both parental alleles rather than in cis.Conclusions/Significance
These results support a model in which DMR0 and IC1 have opposite susceptibilities to global hyper and hypomethylation during tumorigenesis independent of the parent of origin imprint. In contrast, during embryogenesis DMR0 is methylated or demethylated according to the germline methylation imprint at the IC1, indicating different mechanisms of imprinting loss in neoplastic and non-neoplastic cells. 相似文献98.
Lin JL Radajewski S Eshinimaev BT Trotsenko YA McDonald IR Murrell JC 《Environmental microbiology》2004,6(10):1049-1060
Soda lakes are an environment with an unusually high pH and often high salinity. To identify the active methanotrophs in the Soda lake sediments, sediment slurries were incubated with a 10% (v/v) (13)CH(4) headspace and the (13)C-labelled DNA was subsequently extracted from these sediments following CsCl density gradient centrifugation. This DNA was then used as a template for PCR amplification of 16S rRNA genes and genes encoding PmoA and MmoX of methane monooxygenase, key enzymes in the methane oxidation pathway. Phylogenetic analysis of 16S rRNA genes, PmoA and MmoX identified that strains of Methylomicrobium, Methylobacter, Methylomonas and 'Methylothermus' had assimilated the (13)CH(4). Phylogenetic analysis of PmoA sequences amplified from DNA extracted from Soda lake sediments before Stable Isotope Probing (SIP) treatment showed that a much wider diversity of both type I and type II methanotroph sequences are present in this alkaline environment. The majority of methanotroph sequences detected in the (13)C-DNA studies were from type I methanotrophs, with 50% of 16S rRNA clones and 100% of pmoA clones from both Lake Suduntuiskii Torom and Lake Gorbunka suggesting that the type I methanotrophs are probably responsible for the majority of methane oxidation in this environment. 相似文献
99.
Detection of Methane Oxidizing Bacteria in Forest Soil by Monooxygenase PCR Amplification 总被引:5,自引:0,他引:5
100.
Crude and immunoaffinity-purified excretory-secretory antigens derived from a domestic pig isolate of Trichinella spiralis were used in an enzyme-linked immunosorbent assay to test serum from mice infected with 25 different pig and wild animal isolates of T. spiralis sspp. All of the sera were found positive by ELISA using either of the antigen preparations, indicating all isolates shared certain antigen epitopes. Excretory-secretory antigens were prepared from 3 distinct isolates of T. spiralis sspp.--Trichinella spiralis spiralis (pig isolate), Trichinella spiralis nativa (polar bear isolate), and Trichinella spiralis pseudospiralis--and compared by electrophoresis and monoclonal antibody binding. While protein profiles varied among the isolates, a monoclonal antibody recognizing a major immunodiagnostic antigen epitope bound all 3 antigen preparations. However, this antigen epitope occurred on different molecular weight excretory-secretory proteins from the different isolates. 相似文献