全文获取类型
收费全文 | 263篇 |
免费 | 27篇 |
出版年
2019年 | 2篇 |
2018年 | 3篇 |
2017年 | 5篇 |
2016年 | 10篇 |
2015年 | 15篇 |
2014年 | 14篇 |
2013年 | 10篇 |
2012年 | 12篇 |
2011年 | 8篇 |
2010年 | 15篇 |
2009年 | 13篇 |
2008年 | 6篇 |
2007年 | 5篇 |
2006年 | 14篇 |
2005年 | 11篇 |
2004年 | 7篇 |
2003年 | 3篇 |
2002年 | 5篇 |
2001年 | 7篇 |
2000年 | 10篇 |
1999年 | 8篇 |
1998年 | 9篇 |
1997年 | 7篇 |
1996年 | 8篇 |
1995年 | 3篇 |
1994年 | 7篇 |
1993年 | 3篇 |
1992年 | 4篇 |
1991年 | 4篇 |
1990年 | 2篇 |
1988年 | 2篇 |
1987年 | 4篇 |
1986年 | 4篇 |
1984年 | 6篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1980年 | 5篇 |
1978年 | 2篇 |
1977年 | 4篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1973年 | 5篇 |
1972年 | 2篇 |
1970年 | 3篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1965年 | 1篇 |
1954年 | 1篇 |
1934年 | 1篇 |
排序方式: 共有290条查询结果,搜索用时 31 毫秒
11.
The Tau/A152T mutation,a risk factor for frontotemporal‐spectrum disorders,leads to NR2B receptor‐mediated excitotoxicity
下载免费PDF全文
![点击此处可从《EMBO reports》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Astrid Sydow Frank JA Dennissen Zuzana Siskova Eckhard Mandelkow Eva‐Maria Mandelkow 《EMBO reports》2016,17(4):552-569
We report on a novel transgenic mouse model expressing human full‐length Tau with the Tau mutation A152T (hTauAT), a risk factor for FTD‐spectrum disorders including PSP and CBD. Brain neurons reveal pathological Tau conformation, hyperphosphorylation, mis‐sorting, aggregation, neuronal degeneration, and progressive loss, most prominently in area CA3 of the hippocampus. The mossy fiber pathway shows enhanced basal synaptic transmission without changes in short‐ or long‐term plasticity. In organotypic hippocampal slices, extracellular glutamate increases early above control levels, followed by a rise in neurotoxicity. These changes are normalized by inhibiting neurotransmitter release or by blocking voltage‐gated sodium channels. CA3 neurons show elevated intracellular calcium during rest and after activity induction which is sensitive to NR2B antagonizing drugs, demonstrating a pivotal role of extrasynaptic NMDA receptors. Slices show pronounced epileptiform activity and axonal sprouting of mossy fibers. Excitotoxic neuronal death is ameliorated by ceftriaxone, which stimulates astrocytic glutamate uptake via the transporter EAAT2/GLT1. In summary, hTauAT causes excitotoxicity mediated by NR2B‐containing NMDA receptors due to enhanced extracellular glutamate. 相似文献
12.
Hernandez-Trejo A B Estrada-Drouaillet JA López-Santillán C Rios-Velasco SE Varela-Fuentes R Rodríguez-Herrera E Osorio-Hernández 《Phyton》2019,88(1):47-54
The control of Spodoptera frugiperda is based
on synthetic insecticides, so some alternatives are the use of
entomopathogenic fungi (EF) and neem extract. The objective of
the study was to evaluate in vitro effectiveness of native EF and
neem extracts on S. frugiperda larvae. Six EF were identified by
DNA sequencing of ITS regions from three EF (Fusarium solani,
Metarrhizium robertsii, Nigrospora spherica and Penicillium
citrinum). They were evaluated in concentrations of 1 × 10⁸ spores/
mL. In addition, a second bioassay was carried out evaluating
only F. solani, M. robertsii and N. sphaerica and the addition
of vegetable oil. On the other hand, extraction of secondary
metabolites from neem seed (Azadirachta indica) was carried
out by performing, mass (g) and solvent volume (mL ethanol
and water) combinations, which were subjected to microwaves
and ultrasound. Subsequently, these extracts were evaluated
in concentrations of 3%, 4% and 5%. A survival analysis was
performed for each of the bioassays. With respect to the results
of the first bioassay, F. solani obtained a probability of survival of
0.476 on the seventh day, while in the second bioassay, M. robertsii
obtained 0.488 survival probability. This suggests that the expected
percentage of larvae that stay alive on the sixth day is 48.8%.
However, in the evaluation of the neem extract the combination
1:12/70% to 4% caused 84% mortality of larvae. The use of native
HE and neem extracts has potential for the control of S. frugiperda. 相似文献
13.
A continuous-flow competitive exclusion (CFCE) culture model of human stool microflora was used to examine whether supplemental anaerobic gas is necessary for maintenance of anaerobes and inhibition of vancomycin-resistant Enterococcus (VRE). CFCE cultures of human stool microflora were maintained with supplemental nitrogen, without supplemental nitrogen, or with percolated room air. Cultures with or without supplemental nitrogen maintained >9 log10 CFU mL–1 of obligate anaerobes and eliminated 106 CFU mL–1 of VRE. When room air was percolated into the culture, anaerobes were detected at 2 log10 CFU mL–1, and the same VRE inoculum was not eliminated (P < 0.001). These data demonstrate that human stool CFCE cultures maintain high levels of obligate anaerobes and inhibit VRE without the addition of supplemental anaerobic gas. 相似文献
14.
15.
Arbing MA Dahan D Boismenu D Mamer OA Hanrahan JW Coulton JW 《The Journal of membrane biology》2000,178(3):185-193
Porin of Haemophilus influenzae type b (341 amino acids; M
r
37782) determines the permeability of the outer membrane to low molecular mass compounds. Purified Hib porin was subjected
to chemical modification of lysine residues by succinic anhydride. Electrospray ionization mass spectrometry identified up
to 12 modifications per porin molecule. Tryptic digestion of modified Hib porin followed by reverse phase chromatography and
matrix assisted laser desorption ionization time-of-flight mass spectrometry mapped the succinylation sites. Most modified
lysines are positioned in surface-located loops, numbers 1 and 4 to 7. Succinylated porin was reconstituted into planar lipid
bilayers, and biophysical properties were analyzed and compared to Hib porin: there was an increased average single channel
conductance compared to Hib porin (1.24+/−0.41 vs. 0.85+/−0.40 nanosiemens). The voltage-gating activity of succinylated porin differed considerably from that of Hib porin.
The threshold voltage for gating was decreased from 75 to 40 mV. At 80 mV, steady-state conductance for succinylated porin
was 50–55% of the instantaneous conductance. Hib porin at 80 mV showed a decrease to 89–91% of the instantaneous current levels.
We propose that surface-located lysine residues are determinants of voltage gating for porin of Haemophilus influenzae type b.
Received: 11 August 2000/Revised: 8 September 2000 相似文献
16.
17.
18.
19.
20.
2’-Methoxy-6-methylflavone (2’MeO6MF) is an anxiolytic flavonoid which has been shown to display GABAA receptor (GABAAR) β2/3-subunit selectivity, a pharmacological profile similar to that of the general anaesthetic etomidate. Electrophysiological studies suggest that the full agonist action of 2’MeO6MF at α2β3γ2L GABAARs may mediate the flavonoid’s in vivo effects. However, we found variations in the relative efficacy of 2’MeO6MF (2’MeO6MF-elicited current responses normalised to the maximal GABA response) at α2β3γ2L GABAARs due to the presence of mixed receptor populations. To understand which receptor subpopulation(s) underlie the variations observed, we conducted a systematic investigation of 2’MeO6MF activity at all receptor combinations that could theoretically form (α2, β3, γ2L, α2β3, α2γ2L, β3γ2L and α2β3γ2L) in Xenopus oocytes using the two-electrode voltage clamp technique. We found that 2’MeO6MF activated non-α-containing β3γ2L receptors. In an attempt to establish the optimal conditions to express a uniform population of these receptors, we found that varying the relative amounts of β3:γ2L subunit mRNAs resulted in differences in the level of constitutive activity, the GABA concentration-response relationships, and the relative efficacy of 2’MeO6MF activation. Like 2’MeO6MF, general anaesthetics such as etomidate and propofol also showed distinct levels of relative efficacy across different injection ratios. Based on these results, we infer that β3γ2L receptors may form with different subunit stoichiometries, resulting in the complex pharmacology observed across different injection ratios. Moreover, the discovery that GABA and etomidate have direct actions at the α-lacking β3γ2L receptors raises questions about the structural requirements for their respective binding sites at GABAARs. 相似文献