全文获取类型
收费全文 | 876篇 |
免费 | 64篇 |
出版年
2023年 | 3篇 |
2022年 | 8篇 |
2021年 | 27篇 |
2020年 | 6篇 |
2019年 | 12篇 |
2018年 | 9篇 |
2017年 | 16篇 |
2016年 | 26篇 |
2015年 | 37篇 |
2014年 | 43篇 |
2013年 | 81篇 |
2012年 | 89篇 |
2011年 | 79篇 |
2010年 | 51篇 |
2009年 | 37篇 |
2008年 | 67篇 |
2007年 | 60篇 |
2006年 | 49篇 |
2005年 | 53篇 |
2004年 | 49篇 |
2003年 | 47篇 |
2002年 | 39篇 |
2001年 | 5篇 |
2000年 | 1篇 |
1999年 | 6篇 |
1998年 | 8篇 |
1997年 | 8篇 |
1996年 | 2篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1981年 | 3篇 |
1976年 | 1篇 |
排序方式: 共有940条查询结果,搜索用时 46 毫秒
131.
In this paper a new nanostructured support for the culture of cells is presented. The support consists of fields of sharp
and high-aspect-ratio nanoneedles. The support is obtained through a specifically developed process that allows controlling
the nanoneedles’s densities and height. The nanoneedles are typically 10 μm high with tip diameters under 200 nm. Cell viability
on this support was evaluated through long-term cells cultures. The narrow interface between the cells’ membrane and the nanoneedles
has been carefully observed to conclude on the perforation of the cells’ membrane thanks to the sharp nanoneedles. Such a
nanostructured chip, allowing specific interaction, opens the door to a large number of exciting and valuable applications
such as nanoporation for transfection or internal cell potential recording. 相似文献
132.
Simulation of potential range expansion of oak disease caused by Phytophthora cinnamomi under climate change 总被引:1,自引:0,他引:1
Magali Bergot Emmanuel Cloppet Victorine Pérarnaud† Michel Déqué‡ Benoît Marçais§ Marie-Laure Desprez-Loustau¶ 《Global Change Biology》2004,10(9):1539-1552
This study examines the effects of climate warming on one of the most widely distributed and destructive forest pathogens, Phytophthora cinnamomi. In Europe, the winter survival of the pathogen is the dominant cue for the development of the disease it causes to oaks, especially Quercus robur and Q. rubra. The potential pathogen and disease geographic ranges were compared in France between two reference periods, 1968–1998 and 2070–2099. Simulations were obtained by combining a physiologically based approach predicting the pathogen winter survival in relation to microhabitat temperature (in the phloem of infected trees) with a regionalized climatic scenario derived from a global circulation model. Positive anomalies in winter temperatures calculated with this scenario were in the range 0.5–5°C between the periods 2070–2099 and the 1968–1998, according to sites and months. As a consequence, higher annual rates of P. cinnamomi survival were predicted, resulting in a potential range expansion of the disease of one to a few hundred kilometers eastward from the Atlantic coast within one century. Based on this example, the study emphasizes the need of a better understanding of the impacts of global change on the biotic constraint constituted by plant pathogens. 相似文献
133.
We used real-time atomic force microscopy (AFM) to visualize the interactions between supported lipid membranes and well-defined surfactin analogs, with the aim to understand the influence of geometry, charge and hydrophobicity. AFM images of mixed dioleoylphosphatidylcholine/dipalmitoylphosphatidylcholine (DOPC/DPPC) bilayers recorded after injection of cyclic surfactin at 1 mM, i.e. well-above the critical micelle concentration, revealed a complete solubilization of the bilayers within 30 min. A linear analog having the same charge and acyl chains was able to solubilize DOPC, but not DPPC, and to promote redeposition leading eventually to a new bilayer. Increasing the charge of the polar head or the length of the acyl chains of the analogs lead to the complete solubilization of both DOPC and DPPC, thus to a stronger membrane activity. Lastly, we found that at low surfactin concentrations (40 µM), DPPC domains were always resistant to solubilization. These data demonstrate the crucial role played by geometry, charge and hydrophobicity in modulating the membrane activity (solubilization, redeposition) of surfactin. Also, this study suggests that synthetic analogs are excellent candidates for developing new surfactants with tunable, well-defined properties for medical and biotechnological applications. 相似文献
134.
Bridget E Berechid Magali Kitzmann Daniel R Foltz Arthur H Roach Dietmar Seiffert Lorin A Thompson Richard E Olson Alan Bernstein Dorit B Donoviel Jeffrey S Nye 《The Journal of biological chemistry》2002,277(10):8154-8165
Presenilin (PS) proteins control the proteolytic cleavage that precedes nuclear access of the Notch intracellular domain. Here we observe that a partial activation of the HES1 promoter can be detected in PS1/PS2 (PS1/2) double null cells using Notch1 Delta E constructs or following Delta 1 stimulation, despite an apparent abolition of the production and nuclear accumulation of the Notch intracellular domain. PS1/2-independent Notch activation is sensitive to Numblike, a physiological inhibitor of Notch. PS1/2-independent Notch signaling is also inhibited by an active gamma-secretase inhibitor in the low micromolar range and is not inhibited by an inactive analogue, similar to PS-dependent Notch signaling. However, experiments using a Notch1-Gal4-VP16 fusion protein indicate that the PS1/2-independent activity does not release Gal4-VP16 and is therefore unlikely to proceed via an intramembranous cleavage. These data reveal that a novel PS1/2-independent mechanism plays a partial role in Notch signal transduction. 相似文献
135.
Daniel De Vos Magali De Chial Christel Cochez Silke Jansen Burkhard Tümmler Jean-Marie Meyer Pierre Cornelis 《Archives of microbiology》2001,175(5):384-388
The lungs of cystic fibrosis patients are frequently colonized by Pseudomonas aeruginosa, which produces high-affinity fluorescent peptidic siderophores, pyoverdines. Three pyoverdines which differ in their peptide chain and are easily differentiated by isoelectric focusing exist, only one being produced by a given strain. P. aeruginosa isolates from cystic fibrosis patients of a German hospital were analyzed by sequential, pulse-field gel electrophoresis (PFGE) and for pyoverdine production and type. Only producers of type I and type II pyoverdine were found. There was a perfect correlation between the type of pyoverdine produced and the clonality determined by PFGE. PFGE clone C, the most prevalent among cystic fibrosis patients, and found in an aquatic environment, produced type II pyoverdine. Pyoverdine-negative mutants seemed to increase as a function of the lung colonization time, but retained the capacity to take up pyoverdines. Most isolates that took up type II pyoverdine were also able to utilize type I pyoverdine as judged by growth stimulation experiments. No correlation was observed between the loss of pyoverdine production and mucoidy. 相似文献
136.
Estelle Bonnin Luc Saulnier Magali Brunel Ccile Marot Laurence Lesage-Meessen Marcel Asther Jean-Franois Thibault 《Enzyme and microbial technology》2002,31(7):153-1005
Aspergillus niger I-1472 was grown on sugar beet pulp to produce cell wall polysaccharide-degrading enzymes, including feruloyl esterases. Compared to enzymatic activities measured in commercially available mixtures previously used for the release of ferulic acid, the A. niger enzymes were more various. These enzymes were tested to release ferulic acid from sugar beet pulp, maize bran, or autoclaved maize bran. They were as efficient as the commercial mixture to release ferulic acid from sugar beet pulp. On the other hand, they were much more efficient to release ferulic acid from maize bran after autoclaving pretreatment, as 95% of ferulic acid ester were solubilized. Thus, A. niger enzymes exhibited a high interest in the release of ferulic acid from various agro-industrial by-products. 相似文献
137.
Loys Bodin Magali SanCristobal Frédéric Lecerf Philippe Mulsant Bernard Bibé Daniel Lajous Jean-Pierre Belloc Francis Eychenne Yves Amigues Jean-Michel Elsen 《遗传、选种与进化》2002,34(4):447-464
Inheritance of the ovulation rate (OR) in the Lacaune meat breed was studied through records from a small nucleus of 36 hyper-prolific ewes screened on farms on the basis of their natural litter size, and from progeny data of three selected Lacaune sires. These sires were chosen at the AI centre according to their breeding values estimated for the mean and the variability of their daughters'' litter size. Non-carrier Lacaune dairy ewes were inseminated to produce 121 F1 daughters and 27 F1 sons. Twelve sons (four from each sire) were used in turn to inseminate non-carrier Lacaune dairy ewes providing 260 BC progeny ewes. F1 and BC progeny were brought from private farms and gathered after weaning on an experimental farm where ovulation rates were recorded in the first and second breeding seasons. With an average of 6.5 records each, the mean OR of hyper-prolific ewes was very high (5.34), and 38.4% of records showed a rate of 6 or more. F1 data showed high repeatability of OR (r = 0.54) within ewe, with significant variability among ewes. High OR (≥ 4) were observed in each family. A segregation analysis provided a significant likelihood ratio and classified the three founders as heterozygous. BC ewes also displayed high repeatability of OR (r = 0.47) and the mean OR varied considerably between families (from 1.24 to 1.78). Seven of the 12 BC families presented high-ovulating ewes (at least one record ≥ 4) and segregation analysis yielded a highly significant likelihood ratio as compared to an empirical test distribution. The high variability of the mean ovulation rate shown by a small group of daughters of BC ewes inseminated by putative carrier F1 rams, and the very high ovulation rate observed for some of these ewe lambs, confirmed the segregation of a major gene with two co-dominant alleles borne by an autosome. The difference between homozygous non-carriers and heterozygous ewes was about one ovulation on the observed scale and 2.2 standard deviations on the underlying scale. 相似文献
138.
The homodyne light-scattering autocorrelation function originating in translational diffusion has been simulated for a polymerization model proposed for a number of self-associating systems: the sequential addition of identical monomer units to a growing aggregate, with identical equilibrium constants for each step. Both spherical and rigid rod structures have been considered. When applied to quasi-elastic light scattering data on glutamate dehydrogenase self-assembly, the simulation results indicate the formation of elongated polymers having equivalent and identical association sites. The weak response of translational diffusion coefficients to solution non-ideality leads to a valuable test of the unique equilibrium constant assumption. On the other hand, it is shown that successful exploitation of quasi-elastic light scattering data on aggregating systems of this type relies heavily on independent information. 相似文献
139.
Aurélien Sokal Pascal Chappert Giovanna Barba-Spaeth Anais Roeser Slim Fourati Imane Azzaoui Alexis Vandenberghe Ignacio Fernandez Annalisa Meola Magali Bouvier-Alias Etienne Crickx Asma Beldi-Ferchiou Sophie Hue Laetitia Languille Marc Michel Samia Baloul France Noizat-Pirenne Marine Luka Matthieu Mahévas 《Cell》2021,184(5):1201-1213.e14
140.
Early Deficits in Glycolysis Are Specific to Striatal Neurons from a Rat Model of Huntington Disease
Caroline Gouarné Gwena?lle Tardif Jennifer Tracz Virginie Latyszenok Magali Michaud Laura Emily Clemens Libo Yu-Taeger Huu Phuc Nguyen Thierry Bordet Rebecca M. Pruss 《PloS one》2013,8(11)
In Huntington disease (HD), there is increasing evidence for a link between mutant huntingtin expression, mitochondrial dysfunction, energetic deficits and neurodegeneration but the precise nature, causes and order of these events remain to be determined. In this work, our objective was to evaluate mitochondrial respiratory function in intact, non-permeabilized, neurons derived from a transgenic rat model for HD compared to their wild type littermates by measuring oxygen consumption rates and extracellular acidification rates. Although HD striatal neurons had similar respiratory capacity as those from their wild-type littermates when they were incubated in rich medium containing a supra-physiological glucose concentration (25 mM), pyruvate and amino acids, respiratory defects emerged when cells were incubated in media containing only a physiological cerebral level of glucose (2.5 mM). According to the concept that glucose is not the sole substrate used by the brain for neuronal energy production, we provide evidence that primary neurons can use lactate as well as pyruvate to fuel the mitochondrial respiratory chain. In contrast to glucose, we found no major deficits in HD striatal neurons’ capacity to use pyruvate as a respiratory substrate compared to wild type littermates. Additionally, we used extracellular acidification rates to confirm a reduction in anaerobic glycolysis in the same cells. Interestingly, the metabolic disturbances observed in striatal neurons were not seen in primary cortical neurons, a brain region affected in later stages of HD. In conclusion, our results argue for a dysfunction in glycolysis, which might precede any defects in the respiratory chain itself, and these are early events in the onset of disease. 相似文献