全文获取类型
收费全文 | 241篇 |
免费 | 28篇 |
国内免费 | 1篇 |
出版年
2021年 | 6篇 |
2020年 | 2篇 |
2019年 | 5篇 |
2018年 | 6篇 |
2017年 | 8篇 |
2016年 | 10篇 |
2015年 | 15篇 |
2014年 | 17篇 |
2013年 | 16篇 |
2012年 | 13篇 |
2011年 | 18篇 |
2010年 | 7篇 |
2009年 | 11篇 |
2008年 | 6篇 |
2007年 | 18篇 |
2006年 | 2篇 |
2005年 | 3篇 |
2004年 | 6篇 |
2003年 | 4篇 |
2002年 | 5篇 |
2001年 | 8篇 |
2000年 | 6篇 |
1999年 | 4篇 |
1998年 | 2篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1992年 | 6篇 |
1990年 | 3篇 |
1988年 | 4篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1979年 | 3篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1971年 | 3篇 |
1970年 | 3篇 |
1969年 | 3篇 |
1968年 | 1篇 |
1967年 | 2篇 |
1965年 | 1篇 |
排序方式: 共有270条查询结果,搜索用时 218 毫秒
191.
Molecular evolution of chloroplast DNA sequences 总被引:13,自引:1,他引:12
Comparative data on the evolution of chloroplast genes are reviewed. The
chloroplast genome has maintained a similar structural organization over
most plant taxa so far examined. Comparisons of nucleotide sequence
divergence among chloroplast genes reveals marked similarity across the
plant kingdom and beyond to the cyanobacteria (blue-green algae). Estimates
of rates of nucleotide substitution indicate a synonymous rate of 1.1 x
10(-9) substitutions per site per year. Noncoding regions also appear to be
constrained in their evolution, although addition/deletion events are
common. There have also been evolutionary changes in the distribution of
introns in chloroplast encoded genes. Relative to mammalian mitochondrial
DNA, the chloroplast genome evolves at a conservative rate.
相似文献
192.
193.
High nucleotide sequence variation in a region of low recombination in Drosophila simulans is consistent with the background selection model 总被引:2,自引:0,他引:2
We surveyed nucleotide sequence variation at glucose dehydrogenase (Gld),
in a region of low recombination on chromosome 3R, from a population sample
of Drosophila simulans. The levels of nucleotide variation were
surprisingly high. There was no departure from the expectation of a neutral
model for the level of polymorphism, indicating no evidence of a selective
sweep in this region. There was a significant deficiency of singleton
polymorphisms according to the Fu and Li test, although Tajima and Hudson,
Kreitman, and Aguade (HKA) tests do not provide evidence of a significant
elevation of variation due to balancing selection. Genetic map data for the
D. simulans third chromosome were used to calculate expected values of pi
for Gld under a current model of background selection, varying the values
for the parameter sh (selection coefficient against deleterious mutations).
We show that the recombinational landscape of D. simulans is sufficiently
different from that of D. melanogaster that we expect higher variation
under the background selection model, even when effective population sizes
are assumed to be equal. The data for Gld were tested against the
predictions using computer simulations of the distribution of the number of
segregating sites conditioned on pi. Background selection alone can explain
our observations as long as sh is larger than 0.005 and species-level
effective population size is assumed to be several- fold larger than in D.
melanogaster. Alternatively, the deleterious mutation rate may be smaller
in D. simulans, or balancing selection may be acting nearby, thereby
reducing the effect of background selection.
相似文献
194.
Comparative evolutionary analysis of rDNA ITS regions in Drosophila 总被引:17,自引:2,他引:15
Schlotterer C; Hauser MT; von Haeseler A; Tautz D 《Molecular biology and evolution》1994,11(3):513-522
The internal transcribed spacer (ITS) of the ribosomal DNA is generally
considered to be under low functional constraint, and it is therefore often
treated as a typical nonfunctional spacer sequence. We have analyzed the
ITS regions of five species from the Drosophila melanogaster subgroup, two
Drosophila species from outside this group (D. pseudoobscura and D.
virilis), as well as from the more distantly related dipteran fly Musca
domestica. The sequence comparisons show a distinctive
conservation/divergence pattern, indicating that some regions are more
conserved than others. Moreover, secondary-structure calculations indicate
several conserved structural elements within the ITS regions. On the other
hand, a statistical test that allows us to estimate the fraction of sites
that are not under selective constraint suggests that more than half of the
spacer is apparently free to diverge and evolves with a rate that is close
to the neutral rate of sequence evolution in Drosophila. The ITS sequences
can be used to derive a molecular phylogeny for the species under study. We
find that the ITS tree is largely in line with the so-far-known phylogeny
of this group of species, with one difference. The species most distant
within the D. melanogaster subgroup is D. yakuba, rather than D. orena, as
is normally assumed.
相似文献
195.
196.
Glioblastoma is the deadliest brain tumor in humans. Current therapies are mostly ineffective and new agents need to be explored
for controlling this devastating disease. Inositol hexaphosphate (IP6) is a phytochemical that is widely found in corns, cereals,
nuts, and high fiber-content foods. Previous studies demonstrated anti-cancer properties of IP6 in several in vitro and in
vivo tumor models. However, therapeutic efficacy of IP6 has not yet been evaluated in glioblastoma. Here, we explored the
molecular mechanism of action of IP6 in human malignant glioblastoma T98G cells. The viability of T98G cells decreased following
treatment with increasing doses of IP6. T98G cells exposed to 0.25, 0.5, and 1 mM IP6 for 24 h showed morphological and biochemical
features of apoptosis. Western blotting indicated changes in expression of Bax and Bcl-2 proteins resulting in an increase
in Bax:Bcl-2 ratio and upregulation of cytosolic levels of cytochrome c and Smac/Diablo, suggesting involvement of mitochondria-dependent
caspase cascade in apoptosis. IP6 downregulated cell survival factors such as baculovirus inhibitor-of-apoptosis repeat containing-2
(BIRC-2) protein and telomerase to promote apoptosis. Upregulation of calpain and caspase-9 occurred in course of apoptosis.
Increased activities of calpain and caspase-3 cleaved 270 kD α-spectrin at specific sites generating 145 kD spectrin break
down product (SBDP) and 120 kD SBDP, respectively. Increased caspase-3 activity also cleaved inhibitor of caspase-3-activated
DNase and poly(ADP-ribose) polymerase. Collectively, our results demonstrated that IP6 down regulated the survival factors
BIRC-2 and telomerase and upregulated calpain and caspase-3 activities for apoptosis in T98G cells.
Special issue in honor of Naren Banik. 相似文献
197.
Michelle A. Jusino Mark T. Banik Jonathan M. Palmer Amy K. Wray Lei Xiao Emma Pelton Jesse R. Barber Akito Y. Kawahara Claudio Gratton M. Zachariah Peery Daniel L. Lindner 《Molecular ecology resources》2019,19(1):176-190
DNA analysis of predator faeces using high‐throughput amplicon sequencing (HTS) enhances our understanding of predator–prey interactions. However, conclusions drawn from this technique are constrained by biases that occur in multiple steps of the HTS workflow. To better characterize insectivorous animal diets, we used DNA from a diverse set of arthropods to assess PCR biases of commonly used and novel primer pairs for the mitochondrial gene, cytochrome oxidase C subunit 1 (COI). We compared diversity recovered from HTS of bat guano samples using a commonly used primer pair “ZBJ” to results using the novel primer pair “ANML.” To parameterize our bioinformatics pipeline, we created an arthropod mock community consisting of single‐copy (cloned) COI sequences. To examine biases associated with both PCR and HTS, mock community members were combined in equimolar amounts both pre‐ and post‐PCR. We validated our system using guano from bats fed known diets and using composite samples of morphologically identified insects collected in pitfall traps. In PCR tests, the ANML primer pair amplified 58 of 59 arthropod taxa (98%), whereas ZBJ amplified 24–40 of 59 taxa (41%–68%). Furthermore, in an HTS comparison of field‐collected samples, the ANML primers detected nearly fourfold more arthropod taxa than the ZBJ primers. The additional arthropods detected include medically and economically relevant insect groups such as mosquitoes. Results revealed biases at both the PCR and sequencing levels, demonstrating the pitfalls associated with using HTS read numbers as proxies for abundance. The use of an arthropod mock community allowed for improved bioinformatics pipeline parameterization. 相似文献
198.
Lawrence G. MillerJr. Jennifer A. Young Swapan K. Ray Guanghu Wang Sharad Purohit Naren L. Banik Somsankar Dasgupta 《Neurochemical research》2017,42(10):2755-2768
Multiple sclerosis (MS) is a demyelinating disorder characterized by massive neurodegeneration and profound axonal loss. Since myelin is enriched with sphingolipids and some of them display toxicity, biological function of sphingolipids in demyelination has been investigated in MS brain tissues. An elevation of sphingosine with a decrease in monoglycosylceramide and psychosine (myelin markers) was observed in MS white matter and plaque compared to normal brain tissue. This indicated that sphingosine toxicity might mediate oligodendrocyte degeneration. To explain the source of sphingosine accumulation, total sphingolipid profile was investigated in Lewis rats after inducing experimental autoimmune encephalomyelitis (EAE) and also in human oligodendrocytes in culture. An intermittent increase in ceramide followed by sphingosine accumulation in EAE spinal cord along with a stimulation of serine-palmitoyltransferase (SPT) activity was observed. Apoptosis was identified in the lumbar spinal cord, the most prominent demyelinating area, in the EAE rats. TNFα and IFNγ stimulation of oligodendrocytes in culture also led to an accumulation of ceramide with an elevation of sphingosine. Ceramide elevation was drastically blocked by myriocin, an inhibitor of SPT, and also by FTY720. Myriocin treatment also protected oligodendrocytes from cytokine mediated apoptosis or programmed cell death. Hence, we propose that sphingosine toxicity may contribute to demyelination in both EAE and MS, and the intermittent ceramide accumulation in EAE may, at least partly, be mediated via SPT activation, which is a novel observation that has not been previously reported. 相似文献
199.
Azizul Haque Mollie Capone Denise Matzelle April Cox Naren L. Banik 《Neurochemical research》2017,42(10):2777-2787
Spinal cord injury (SCI) is a complex debilitating condition leading to permanent life-long neurological deficits. The complexity of SCI suggests that a concerted multi-targeted therapeutic approach is warranted to optimally improve function. Damage to spinal cord is complicated by an increased detrimental response from secondary injury factors mediated by activated glial cells and infiltrating macrophages. While elevation of enolase especially neuron specific enolase (NSE) in glial and neuronal cells is believed to trigger inflammatory cascades in acute SCI, alteration of NSE and its subsequent effects in acute SCI remains unknown. This study measured NSE expression levels and key inflammatory mediators after acute SCI and investigated the role of ENOblock, a novel small molecule inhibitor of enolase, in a male Sprague–Dawley (SD) rat SCI model. Serum NSE levels as well as cytokines/chemokines and metabolic factors were evaluated in injured animals following treatment with vehicle alone or ENOblock using Discovery assay. Spinal cord samples were also analyzed for NSE and MMPs 2 and 9 as well as glial markers by Western blotting. The results indicated a significant decrease in serum inflammatory cytokines/chemokines and NSE, alterations of metabolic factors and expression of MMPs in spinal cord tissues after treatment with ENOblock (100 µg/kg, twice). These results support the hypothesis that activation of glial cells and inflammation status can be modulated by regulation of NSE expression and activity. Analysis of SCI tissue samples by immunohistochemistry confirmed that ENOblock decreased gliosis which may have occurred through reduction of elevated NSE in rats. Overall, elevation of NSE is deleterious as it promotes extracellular degradation and production of inflammatory cytokines/chemokines and metabolic factors which activates glia and damages neurons. Thus, reduction of NSE by ENOblock may have potential therapeutic implications in acute SCI. 相似文献
200.
Bone marrow endothelial progenitor cells activate hepatic stellate cells and aggravate carbon tetrachloride induced liver fibrosis in mice via paracrine factors
下载免费PDF全文
![点击此处可从《Cell proliferation》网站下载免费的PDF全文](/ch/ext_images/free.gif)