全文获取类型
收费全文 | 246篇 |
免费 | 13篇 |
出版年
2023年 | 3篇 |
2022年 | 7篇 |
2021年 | 11篇 |
2020年 | 8篇 |
2019年 | 8篇 |
2018年 | 10篇 |
2017年 | 7篇 |
2016年 | 10篇 |
2015年 | 20篇 |
2014年 | 13篇 |
2013年 | 19篇 |
2012年 | 22篇 |
2011年 | 15篇 |
2010年 | 13篇 |
2009年 | 9篇 |
2008年 | 13篇 |
2007年 | 13篇 |
2006年 | 8篇 |
2005年 | 7篇 |
2004年 | 8篇 |
2003年 | 7篇 |
2002年 | 7篇 |
2001年 | 3篇 |
1999年 | 1篇 |
1991年 | 2篇 |
1989年 | 1篇 |
1985年 | 3篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1974年 | 1篇 |
1967年 | 2篇 |
1965年 | 1篇 |
1962年 | 1篇 |
1960年 | 1篇 |
排序方式: 共有259条查询结果,搜索用时 968 毫秒
51.
Investigations with astroglial cells carry more prominence in drug abuse studies. However, due to earlier perception that
astroglial cells were only passive bystanders in neural signal transmission, not many investigations were conducted on the
toxicity of various abused drugs, like cocaine. The present study was aimed to discern the effect of cocaine on rat astroglioma
cells and analyzed qualitatively for morphological features as well as vacuolation by phase contrast microscope, quantitatively
for cytotoxicity, mitochondrial membrane potential by rhodamine- 123 fluorometric assay, and cell cycle analysis by flow cytometry.
Based on population cell doubling time studies, glial cells were grown in 10% FBS in RPMI 1640 medium and treated with cocaine
for 24 or 48 h. Microscopic assessments clearly demonstrated massive vacuolation and significant disruption at general architecture
of glial cell morphology with cocaine. Chronic cocaine treatment (24 or 48 h) caused significant loss of cell viability. The
sublethal dose of cocaine was found to be 4.307 and 3.794 mM at 24 and 48 h, respectively. Cocaine reduced the mitochondrial
membrane potential in a dose dependent manner with ED50 of 4 mM after 24 h. Cell cycle analysis suggested dual inhibition at G0/G1 and G2/M phases after 24 and 48 h, respectively.
In summary, our findings suggest that cocaine toxicity was due to loss of mitochondrial membrane potential, vacuolation, and
dual inhibition of cell cycle phases. These results may shed light in understanding the onset of some early key events in
cocaine-induced toxicity in glial cells. 相似文献
52.
53.
Adam Javier Martinez Thomas Ogao Onchuru Chantal Selina Ingham Mario Sandoval‐Caldern Hassan Salem Jürgen Deckert Martin Kaltenpoth 《Molecular ecology》2019,28(23):5172-5187
The adaptation of herbivorous insects to new host plants is key to their evolutionary success in diverse environments. Many insects are associated with mutualistic gut bacteria that contribute to the host's nutrition and can thereby facilitate dietary switching in polyphagous insects. However, how gut microbial communities differ between populations of the same species that feed on different host plants remains poorly understood. Most species of Pyrrhocoridae (Hemiptera: Heteroptera) are specialist seed‐feeders on plants in the family Malvaceae, although populations of one species, Probergrothius angolensis, have switched to the very distantly related Welwitschia mirabilis plant in the Namib Desert. We first compared the development and survival of laboratory populations of Pr. angolensis with two other pyrrhocorids on seeds of Welwitschia and found only Pr. angolensis was capable of successfully completing its development. We then collected Pr. angolensis in Namibia from Malvaceae and Welwitschia host plants, respectively, to assess their bacterial and fungal community profiles using high‐throughput amplicon sequencing. Comparison with long‐term laboratory‐reared insects indicated stable associations of Pr. angolensis with core bacteria (Commensalibacter, Enterococcus, Bartonella and Klebsiella), but not with fungi or yeasts. Phylogenetic analyses of core bacteria revealed relationships to other insect‐associated bacteria, but also found new taxa indicating potential host‐specialized nutritional roles. Importantly, the microbial community profiles of bugs feeding on Welwitschia versus Malvaceae revealed stark and consistent differences in the relative abundance of core bacterial taxa that correlate with the host‐plant switch; we were able to reproduce this result through feeding experiments. Thus, a dynamic gut microbiota may provide a means for insect adaptation to new host plants in new environments when food plants are extremely divergent. 相似文献
54.
Glomski IJ Fritz JH Keppler SJ Balloy V Chignard M Mock M Goossens PL 《Cellular microbiology》2007,9(2):502-513
Bacillus anthracis is a sporulating Gram-positive bacterium that causes the disease anthrax. The highly stable spore is the infectious form of the bacterium that first interacts with the prospective host, and thus the interaction between the host and spore is vital to the development of disease. We focused our study on the response of murine splenocytes to the B. anthracis spore by using paraformaldehyde-inactivated spores (FIS), a treatment that prevents germination and production of products associated with vegetative bacilli. We found that murine splenocytes produce IL-12 and IFN-gamma in response to FIS. The IL-12 was secreted by CD11b cells, which functioned to induce the production of IFN-gamma by CD49b (DX5) NK cells. The production of these cytokines by splenocytes was not dependent on TLR2, TLR4, TLR9, Nod1, or Nod2; however, it was dependent on the signalling adapter protein MyD88. Unlike splenocytes, Nod1- and Nod2-transfected HEK cells were activated by FIS. Both IL-12 and IFN-gamma secretion were inhibited by treatment with B. anthracis lethal toxin. These observations suggest that the innate immune system recognizes spores with a MyD88-dependent receptor (or receptors) and responds by secreting inflammatory cytokines, which may ultimately aid in resisting infection. 相似文献
55.
56.
Mohammed Abul Kashem Selina Ahmed Ranjana SarkerEakhlas U. Ahmed Garth A. HargreavesIain S. McGregor 《Neurochemistry international》2012
Chronic alcohol exposure can adversely affect neuronal morphology, synaptic architecture and associated neuroplasticity. However, the effects of moderate levels of long-term alcohol intake on the brain are a matter of debate. The current study used 2-DE (two-dimensional gel electrophoresis) proteomics to examine proteomic changes in the striatum of male Wistar rats after 8 months of continuous access to a standard off-the-shelf beer in their home cages. Alcohol intake under group-housed conditions during this time was around 3–4 g/kg/day, a level below that known to induce physical dependence in rats. After 8 months of access rats were euthanased and 2-DE proteomic analysis of the striatum was conducted. A total of 28 striatal proteins were significantly altered in the beer drinking rats relative to controls. Strikingly, many of these were dopamine (DA)-related proteins, including tyrosine hydroxylase (an enzyme of DA biosynthesis), pyridoxal phosphate phosphatase (a co-enzyme in DA biosynthesis), DA and cAMP regulating phosphoprotein (a regulator of DA receptors and transporters), protein phosphatase 1 (a signaling protein) and nitric oxide synthase (which modulates DA uptake). Selected protein expression changes were verified using Western blotting. We conclude that long-term moderate alcohol consumption is associated with substantial alterations in the rat striatal proteome, particularly with regard to dopaminergic signaling pathways. This provides potentially important evidence of major neuroadaptations in dopamine systems with daily alcohol consumption at relatively modest levels. 相似文献
57.
58.
The myelin-associated glycoprotein (MAG) is a type I membrane-spanning protein expressed exclusively in oligoden drocytes
and Schwann cells. It has two generally known pathophysiological roles in the central nervous system (CNS): maintenance of
myelin integrity and inhibition of CNS axonal regeneration. The subtle CNS phenotype resulting from genetic ablation of MAG
expression has made mechanistic analysis of its functional role in these difficult. However, the past few years have brought
some major revelations, particularly in terms of mechanisms of MAG signaling through the Nogo-66 receptor (NgR) complex. Although
apparently converging through NgR, a readily noticeable fact is that the neuronal growth inhibitory effect of MAG differs
from that of Nogo-66. This may result from the influence of coreceptors in the form of gangliosides or from MAG-specific neuronal
receptors such as NgR2. MAG has several other neuronal binding partners, and some of these may modulate its interaction with
the NgR complex or downstream signaling. This article discusses new findings in MAG-forward and-reverse signaling and its
role in CNS pathophysiology. 相似文献
59.
Weterings JJ Khan S van der Heden GJ Drijfhout JW Melief CJ Overkleeft HS van der Burg SH Ossendorp F van der Marel GA Filippov DV 《Bioorganic & medicinal chemistry letters》2006,16(12):3258-3261
The preparation of three different 2-alkoxy-8-hydroxyadenylpeptide conjugates has been accomplished by solid-phase synthesis combined with 'on-resin' Cu(I) catalyzed Huisgen cycloaddition. The immunogenicity of the compounds has been evaluated in IL-12 production and antigen presentation assays. 相似文献
60.
Neekesh V Dharia Amar Bir Singh Sidhu María Belén Cassera Scott J Westenberger Selina ER Bopp Rich T Eastman David Plouffe Serge Batalov Daniel J Park Sarah K Volkman Dyann F Wirth Yingyao Zhou David A Fidock Elizabeth A Winzeler 《Genome biology》2009,10(2):R21-13