全文获取类型
收费全文 | 111篇 |
免费 | 11篇 |
出版年
2022年 | 2篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 6篇 |
2017年 | 3篇 |
2016年 | 5篇 |
2015年 | 4篇 |
2014年 | 8篇 |
2013年 | 6篇 |
2012年 | 8篇 |
2011年 | 10篇 |
2010年 | 6篇 |
2009年 | 5篇 |
2008年 | 11篇 |
2007年 | 7篇 |
2006年 | 3篇 |
2005年 | 4篇 |
2004年 | 2篇 |
2003年 | 4篇 |
2002年 | 3篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1991年 | 1篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1980年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有122条查询结果,搜索用时 55 毫秒
51.
Polymorphism and divergence at the 5' flanking region of the sex- determining locus, Sry, in mice 总被引:3,自引:0,他引:3
We have investigated patterns of evolution in the nonrecombining portion of
the Y chromosome in mice by comparing levels of polymorphism within Mus
domesticus with levels of divergence between M. domesticus and M. spretus.
A 1,277-bp fragment of noncoding sequence flanking the sex determining
locus (Sry) was PCR amplified, and 1,063 bases were sequenced and compared
among 20 M. domesticus and 1 M. spretus. Two polymorphic base substitutions
and two polymorphic insertion/deletion sites were identified within M.
domesticus; nucleotide diversity was estimated to be 0.1%. Divergence
between M. domesticus and M. spretus for this region (1.9%) was slightly
lower than the average divergence of single-copy nuclear DNA for these
species. Comparison of levels of polymorphism and divergence at Sry with
levels of polymorphism and divergence in the mitochondrial DNA control
region provided no evidence of a departure from the expectations of neutral
molecular evolution. These findings are consistent with the presumed lack
of function for much of the Y chromosome.
相似文献
52.
53.
Goldstein DB; Zhivotovsky LA; Nayar K; Linares AR; Cavalli-Sforza LL; Feldman MW 《Molecular biology and evolution》1996,13(9):1213-1218
It has recently been suggested that observed levels of variation at
microsatellite loci can be used to infer patterns of selection in genomes
and to assess demographic history. In order to evaluate the feasibility of
these suggestions it is necessary to know something about how levels of
variation at microsatellite loci are expected to fluctuate due simply to
stochasticity in the processes of mutation and inheritance (genetic
sampling). Here we use recently derived properties of the stepwise mutation
model to place confidence intervals around the variance in repeat score
that is expected at mutation-drift equilibrium and outline a statistical
test for whether an observed value differs significantly from expectation.
We also develop confidence intervals for the time course of the buildup of
variation following a complete elimination of variation, such as might be
caused by a selective sweep or an extreme population bottleneck. We apply
these methods to the variation observed at human Y-specific
microsatellites. Although a number of authors have suggested the
possibility of a very recent sweep, our analyses suggest that a sweep or
extreme bottleneck is unlikely to have occurred anytime during the last
approximately 74,000 years. To generate this result we use a recently
estimated mutation rate for microsatellite loci of 5.6 x 10(-4) along with
the variation observed at autosomal microsatellite loci to estimate the
human effective population size. This estimate is 18,000, implying an
effective number of 4,500 Y chromosomes. One important general conclusion
to emerge from this study is that in order to reject mutation-drift
equilibrium at a set of linked microsatellite loci it is necessary to have
an unreasonably large number of loci unless the observed variance is far
below that expected at mutation-drift equilibrium.
相似文献
54.
Pauline MW van Kempen Rob Noorlag Weibel W Braunius Inge Stegeman Stefan M Willems Wilko Grolman 《Epigenetics》2014,9(2):194-203
Oropharyngeal squamous cell carcinoma (OPSCC) is associated with human papillomavirus (HPV). HPV-positive OPSCC is considered a distinct molecular entity with a better prognosis than HPV-negative cases of OPSCC. However, the exact pathogenic mechanisms underlying the differences in clinical and molecular behavior between HPV-positive and HPV-negative OPSCC remain poorly understood. Epigenetic events play an important role in the development of cancer. Hypermethylation of DNA in promoter regions and global hypomethylation are 2 epigenetic changes that have been frequently observed in human cancers. It is suggested that heterogeneous epigenetic changes play a role in the clinical and biological differences between HPV-positive and HPV-negative tumors. Unraveling the differences in methylation profiles of HPV-associated OPSCC may provide for promising clinical applications and may pave the road for personalized cancer treatment. This systematic review aims to assess the current state of knowledge regarding differences in promoter hypermethylation and global methylation between HPV-positive and HPV-negative OPSCC. 相似文献
55.
Brooke Baldauf McBride Gisèle Muller‐Parker Hans Henrik Jakobsen 《Journal of phycology》2009,45(4):855-863
Symbiodinium californium (#383, Banaszak et al. 1993 ) is one of two known dinoflagellate symbionts of the intertidal sea anemones Anthopleura elegantissima, A. xanthogrammica, and A. sola and occurs only in hosts at southern latitudes of the North Pacific. To investigate if temperature restricts the latitudinal distribution of S. californium, growth and photosynthesis at a range of temperatures (5°C–30°C) were determined for cultured symbionts. Mean specific growth rates were the highest between 15°C and 28°C (μ 0.21–0.26 · d?1) and extremely low at 5, 10, and 30°C (0.02–0.03 · d?1). Average doubling times ranged from 2.7 d (20°C) to 33 d (5, 10, and 30°C). Cells cultured at 10°C had the greatest cell volume (821 μm3) and the highest percentage of motile cells (64.5%). Growth and photosynthesis were uncoupled; light‐saturated maximum photosynthesis (Pmax) increased from 2.9 pg C · cell?1 · h?1 at 20°C to 13.2 pg C · cell?1 · h?1 at 30°C, a 4.5‐fold increase. Less than 11% of daily photosynthetically fixed carbon was utilized for growth at 5, 10, and 30°C, indicating the potential for high carbon translocation at these temperatures. Low temperature effects on growth rate, and not on photosynthesis and cell morphology, may restrict the distribution of S. californium to southern populations of its host anemones. 相似文献
56.
Madeleine SQ Kortenhorst Michel D Wissing Ronald Rodriguez Sushant K Kachhap Judith JM Jans Petra Van der Groep Henk MW Verheul Anuj Gupta Paul O Aiyetan Elsken van der Wall Michael A Carducci Paul J Van Diest Luigi Marchionni 《Epigenetics》2013,8(9):907-920
Histone deacetylases (HDACs) have emerged as important targets for cancer treatment. HDAC-inhibitors (HDACis) are well tolerated in patients and have been approved for the treatment of patients with cutaneous T-cell lymphoma (CTCL). To improve the clinical benefit of HDACis in solid tumors, combination strategies with HDACis could be employed. In this study, we applied Analysis of Functional Annotation (AFA) to provide a comprehensive list of genes and pathways affected upon HDACi-treatment in prostate cancer cells. This approach provides an unbiased and objective approach to high throughput data mining. By performing AFA on gene expression data from prostate cancer cell lines DU-145 (an HDACi-sensitive cell line) and PC3 (a relatively HDACi-resistant cell line) treated with HDACis valproic acid or vorinostat, we identified biological processes that are affected by HDACis and are therefore potential treatment targets for combination therapy. Our analysis revealed that HDAC-inhibition resulted among others in upregulation of major histocompatibility complex (MHC) genes and deregulation of the mitotic spindle checkpoint by downregulation of genes involved in mitosis. These findings were confirmed by AFA on publicly available data sets from HDACi-treated prostate cancer cells. In total, we analyzed 375 microarrays with HDACi treated and non-treated (control) prostate cancer cells. All results from this extensive analysis are provided as an online research source (available at the journal’s website and at http://luigimarchionni.org/HDACIs.html). By publishing this data, we aim to enhance our understanding of the cellular changes after HDAC-inhibition, and to identify novel potential combination strategies with HDACis for the treatment of prostate cancer patients. 相似文献
57.
In late Jan and early Feb 2005 samples for isolation of dictyostelid cellular slime molds (dictyostelids) were collected in five different provinces and from six national parks (all located 39-55°S) in Patagonia and Tierra del Fuego, Argentina. Southern beech (Nothofagus) forests represented the primary vegetation type investigated, but some samples were obtained from Patagonian steppe, alpine meadows, Valdivian temperate rainforests and coniferous forests dominated by Araucaria, Austrocedrus and Fitzroya. Among the dictyostelids isolated from the samples we collected were seven species new to science. These species (Dictyostelium austroandinum, D. chordatum, D. fasciculoideum, D. gargantuum, D. leptosomopsis, D. valdivianum and Polysphondylium patagonicum) are described herein on the basis of both morphology and molecular (SSU rDNA) data. One of the new species, D. gargantuum, is one of the largest representatives of the group reported to date. Another unusual species, D. chordatum, produces long interwoven sorocarps that do not appear to respond to a spacing gas similar to the condition first noted in D. implicatum. 相似文献
58.
Sara MW Hyldig Nicola Croxall David A Contreras Preben D Thomsen Ramiro Alberio 《BMC developmental biology》2011,11(1):11-1
Background
Epigenetic reprogramming is critical for genome regulation during germ line development. Genome-wide demethylation in mouse primordial germ cells (PGC) is a unique reprogramming event essential for erasing epigenetic memory and preventing the transmission of epimutations to the next generation. In addition to DNA demethylation, PGC are subject to a major reprogramming of histone marks, and many of these changes are concurrent with a cell cycle arrest in the G2 phase. There is limited information on how well conserved these events are in mammals. Here we report on the dynamic reprogramming of DNA methylation at CpGs of imprinted loci and DNA repeats, and the global changes in H3K27me3 and H3K9me2 in the developing germ line of the domestic pig. 相似文献59.
Dictyostelid social amoebae are a large and ancient group of soil microbes with an unusual multicellular stage in their life cycle. Taxonomically, they belong to the eukaryotic supergroup Amoebozoa, the sister group to Opisthokonta (animals + fungi). Roughly half of the ~150 known dictyostelid species were discovered during the last five years and probably many more remain to be found. The traditional classification system of Dictyostelia was completely overturned by cladistic analyses and molecular phylogenies of the past six years. As a result, it now appears that, instead of three major divisions there are eight, none of which correspond to traditional higher-level taxa. In addition to the widely studied Dictyostelium discoideum, there are now efforts to develop model organisms and complete genome sequences for each major group. Thus Dictyostelia is becoming an excellent model for both practical, medically related research and for studying basic principles in cell-cell communication and developmental evolution. In this review we summarize the latest information about their life cycle, taxonomy, evolutionary history, genome projects and practical importance. 相似文献
60.
Rogier AM Quax Jan W Koper Pascal HP de Jong Ramona van Heerebeek Angelique E Weel Anne M Huisman Derkjen van Zeben Frank H de Jong Steven WJ Lamberts Johanna MW Hazes Richard A Feelders 《Arthritis research & therapy》2012,14(4):R195