全文获取类型
收费全文 | 416篇 |
免费 | 34篇 |
出版年
2023年 | 4篇 |
2022年 | 3篇 |
2021年 | 15篇 |
2020年 | 5篇 |
2019年 | 2篇 |
2018年 | 6篇 |
2017年 | 6篇 |
2016年 | 13篇 |
2015年 | 22篇 |
2014年 | 13篇 |
2013年 | 24篇 |
2012年 | 25篇 |
2011年 | 30篇 |
2010年 | 18篇 |
2009年 | 14篇 |
2008年 | 25篇 |
2007年 | 21篇 |
2006年 | 21篇 |
2005年 | 21篇 |
2004年 | 27篇 |
2003年 | 17篇 |
2002年 | 15篇 |
2001年 | 13篇 |
2000年 | 7篇 |
1999年 | 9篇 |
1998年 | 5篇 |
1997年 | 7篇 |
1994年 | 3篇 |
1993年 | 4篇 |
1992年 | 3篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 4篇 |
1986年 | 4篇 |
1985年 | 5篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 4篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1971年 | 1篇 |
1969年 | 1篇 |
1967年 | 1篇 |
1965年 | 1篇 |
1923年 | 1篇 |
排序方式: 共有450条查询结果,搜索用时 46 毫秒
71.
Redouane Fodil Lydia Brugel-Ribere Céline Croce Gabriela Sbirlea-Apiou Christian Larger Jean-Fran?ois Papon Christophe Delclaux André Coste Daniel Isabey Bruno Louis 《Journal of applied physiology》2005,98(1):288-295
We have developed a discrete multisegmental model describing the coupling between inspiratory flow and nasal wall distensibility. This model is composed of 14 individualized compliant elements, each with its own relationship between cross-sectional area and transmural pressure. Conceptually, this model is based on flow limitation induced by the narrowing of duct due to collapsing pressure. For a given inspiratory pressure and for a given compliance distribution, this model predicts the area profile and inspiratory flow. Acoustic rhinometry and posterior rhinomanometry were used to determine the initial geometric area and mechanical characteristics of each element. The proposed model, used under steady-state conditions, is able to simulate the pressure-flow relationship observed in vivo under normal conditions (4 subjects) and under pathological conditions (4 vasomotor rhinitis and 3 valve syndrome subjects). Our results suggest that nasal wall compliance is an essential parameter to understand the nasal inspiratory flow limitation phenomenon and the associated increase of resistance that is well known to physiologists. By predicting the functional pressure-flow relationship, this model could be a useful tool for the clinician to evaluate the potential effects of treatments. 相似文献
72.
Nicolas Floquet Antonietta Pepe Manuel Dauchez Brigida Bochicchio Antonio M Tamburro Alain J P Alix 《Matrix biology》2005,24(4):271-282
Elastin macromolecular assembly is a highly complex mechanism involving many steps including coacervation, cross-linking, and probably other (not known) phenomena. In past studies, it has been proposed that the C-terminal part of tropoelastin is also involved in this process and may play a key role in tropoelastin interactions with other proteins of the final elastic fibres scaffold. Presented here are the results of the biophysical studies (biospectroscopy, bioinformatics) of the C-terminal domain of tropoelastin. We report the detailed structures adopted by the oxidized (native) and reduced forms of the free synthetic peptide with sequence encoded by exon 36 of human tropoelastin (GGACLGKACGRKRK) and propose a dynamical interpretation of which structures may be involved in interactions with other extra-cellular matrix proteins. We also suggest that these structures may be retrieved in other proteins sharing a consensus sequence; however no definitive conclusion can be drawn here on a possible structure-function relationship. 相似文献
73.
Maingret F Coste B Hao J Giamarchi A Allen D Crest M Litchfield DW Adelman JP Delmas P 《Neuron》2008,59(3):439-449
Small-conductance Ca2+-activated K+ (SK) channels are widely expressed in neuronal tissues where they underlie post-spike hyperpolarizations, regulate spike-frequency adaptation, and shape synaptic responses. SK channels constitutively interact with calmodulin (CaM), which serves as Ca2+ sensor, and with protein kinase CK2 and protein phosphatase 2A, which modulate their Ca2+ gating. By recording coupled activities of Ca2+ and SK2 channels, we showed that SK2 channels can be inhibited by neurotransmitters independently of changes in the activity of the priming Ca2+ channels. This inhibition involvesSK2-associated CK2 and results from a 3-fold reduction in the Ca2+ sensitivity of channel gating. CK2phosphorylated SK2-bound CaM but not KCNQ2-bound CaM, thereby selectively regulating SK2 channels. We extended these observations to sensory neurons by showing that noradrenaline inhibits SK current and increases neuronal excitability in aCK2-dependent fashion. Hence, neurotransmitter-initiated signaling cascades can dynamically regulate Ca2+ sensitivity of SK channels and directly influence somatic excitability. 相似文献
74.
Martyn Kelly Cathy Bennett Michel Coste Cristina Delgado François Delmas Luc Denys Luc Ector Claude Fauville Martial Ferréol Malgorzata Golub Amelie Jarlman Maria Kahlert John Lucey Bernadette Ní Chatháin Isabel Pardo Peter Pfister Joanna Picinska-Faltynowicz Juliette Rosebery Christine Schranz Jochen Schaumburg Herman van Dam Sirje Vilbaste 《Hydrobiologia》2009,621(1):169-182
The European Union (EU)’s Water Framework Directive (WFD) requires that all Member States participate in intercalibration
exercises in order to ensure that ecological status concepts and assessment levels are consistent across the EU. This paper
describes one such exercise, performed by the countries in the Central/Baltic Geographical Intercalibration Group stretching
from Ireland in the west to Estonia in the east and from the southern parts of Scandinavia to the northern regions of Spain
and Italy (but excluding alpine regions, which were intercalibrated separately). In this exercise, methods used to measure
ecological status of rivers using benthic diatoms were compared. Ecological status is estimated as the ratio between the observed
value of a biological element and the value expected in the absence of significant human impact. Approaches to defining the
‘reference sites’, from which these ‘expected’ values were derived, varied from country to country. Minimum criteria were
established as part of the exercise but there was still considerable variation between national reference values, reflecting
typological differences that could not be resolved during the exercise. A simple multimetric index was developed to compare
boundary values using two widely used diatom metrics. Boundary values for high/good status and good/moderate status set by
each participant were converted to their equivalent values of this intercalibration metric using linear regression. Variation
of ±0.05 EQR units around the median value was considered to be acceptable and the exercise provided a means for those Member
States who fell significantly above or below this line to review their approaches and, if necessary, adjust their boundaries.
Handling editor: J. Padisak 相似文献
75.
In Escherichia coli strains carrying null mutations in either the dnaK or dnaJ genes, the late stages of 30S and 50S ribosomal subunit biogenesis are slowed down in a temperature‐dependent manner. At high temperature (44°C), 32S and 45S particles (precursors to 50S subunits) and 21S particles (precursors to 30S subunits) accumulate. The latter are shown by 3′5′ rapid amplification of cDNA ends analysis to contain unprocessed or partially processed 16S ribosomal RNA at the 5′ end, but the 3′ end was never processed. This implies that maturation of 16S ribosomal RNA starts at the 5′‐terminus, and that the 3′‐terminus is only trimmed at a later step. At normal temperatures (30°C?37°C), ribosome assembly in both mutants is not arrested but is significantly delayed, as shown by pulse‐chase analysis. Assembly defects are partially compensated by an overexpression of other heat‐shock proteins, which occurs in the absence of their negative regulator DnaK, or by a plasmid‐driven overexpression of GroES/GroEL, suggesting the involvement of a network of chaperones in ribosome biogenesis. 相似文献
76.
Christine Decaestecker Xavier Moles Lopez Nicky D'Haene Isabelle Roland Saad Guendouz Christophe Duponchelle Alix Berton Olivier Debeir Isabelle Salmon 《Proteomics》2009,9(19):4478-4494
Antibody‐based proteomics applied to tissue microarray (TMA) technology provides a very efficient means of visualizing and locating antigen expression in large collections of normal and pathological tissue samples. To characterize antigen expression on TMAs, the use of image analysis methods avoids the effects of human subjectivity evidenced in manual microscopical analysis. Thus, these methods have the potential to significantly enhance both precision and reproducibility. Although some commercial systems include tools for the quantitative evaluation of immunohistochemistry‐stained images, there exists no clear agreement on best practices to allow for correct and reproducible quantification results. Our study focuses on practical aspects regarding (i) image acquisition (ii) segmentation of staining and counterstaining areas and (iii) extraction of quantitative features. We illustrate our findings using a commercial system to quantify different immunohistochemistry markers targeting proteins with different expression patterns (cytoplasmic, nuclear or membranous) in colon cancer or brain tumor TMAs. Our investigations led us to identify several steps that we consider essential for standardizing computer‐assisted immunostaining quantification experiments. In addition, we propose a data normalization process based on reference materials to be able to compare measurements between studies involving different TMAs. In conclusion, we recommend certain critical prerequisites that commercial or in‐house systems should satisfy in order to permit valid immunostaining quantification. 相似文献
77.
Virginie Prulière-Escabasse Christine Clerici Grégoire Vuagniaux Andre Coste Estelle Escudier Carole Planès 《Respiratory research》2010,11(1):141
Background
Hyperactivity of the epithelial sodium (Na+) channel (ENaC) and increased Na+ absorption by airway epithelial cells leading to airway surface liquid dehydration and impaired mucociliary clearance are thought to play an important role in the pathogenesis of cystic fibrosis (CF) pulmonary disease. In airway epithelial cells, ENaC is constitutively activated by endogenous trypsin-like serine proteases such as Channel-Activating Proteases (CAPs). It was recently reported that ENaC activity could also be stimulated by apical treatment with human neutrophil elastase (hNE) in a human airway epithelial cell line, suggesting that hNE inhibition could represent a novel therapeutic approach for CF lung disease. However, whether hNE can also activate Na+ reabsorption in primary human nasal epithelial cells (HNEC) from control or CF patients is currently unknown.Methods
We evaluated by short-circuit current (Isc) measurements the effects of hNE and EPI-hNE4, a specific hNE inhibitor, on ENaC activity in primary cultures of HNEC obtained from control (9) and CF (4) patients.Results
Neither hNE nor EPI-hNE4 treatments did modify Isc in control and CF HNEC. Incubation with aprotinin, a Kunitz-type serine protease inhibitor that blocks the activity of endogenous CAPs, decreased Isc by 27.6% and 54% in control and CF HNEC, respectively. In control and CF HNEC pretreated with aprotinin, hNE did significantly stimulate Isc, an effect which was blocked by EPI-hNE4.Conclusions
These results indicate that hNE does activate ENaC and transepithelial Na+ transport in both normal and CF HNEC, on condition that the activity of endogenous CAPs is first inhibited. The potent inhibitory effect of EPI-hNE4 on hNE-mediated ENaC activation observed in our experiments highlights that the use of EPI-hNE4 could be of interest to reduce ENaC hyperactivity in CF airways. 相似文献78.
79.
Florian A. Horenkamp Shaeri Mukherjee Eric Alix Curtis M. Schauder Andree M. Hubber Craig R. Roy Karin M. Reinisch 《Traffic (Copenhagen, Denmark)》2014,15(5):488-499
Tethering proteins play a key role in vesicular transport, ensuring that cargo arrives at a specific destination. The bacterial effector protein SidC and its paralog SdcA have been described as tethering factors encoded by the intracellular pathogen Legionella pneumophila. Here, we demonstrate that SidC proteins are important for early events unique to maturation of vacuoles containing Legionella and discover monoubiquitination of Rab1 as a new SidC‐dependent activity. The crystal structure of the SidC N‐terminus revealed a novel fold that is important for function and could be involved in Legionella adaptations to evolutionarily divergent host cells it encounters in natural environments. 相似文献
80.
Sesamol (3,4-methylenedioxyphenol) at 2.5 mM inhibited growth of Fusarium moniliforme by about 40% and lipid accumulation by 35%. Gibberellin (GA3) accumulation was increased by 20-fold, to 63 mg g–1 biomass, in the presence of sesamol indicating that the acetyl-CoA destined for fatty acid biosynthesis was now being switched into secondary metabolite (GA3) accumulation. Synthesis of other metabolites from acetyl-CoA, such as bikaverin and carotenoids, though were not increased in the presence of sesamol. Metabolic switching is therefore feasible by judicious use of selected inhibitors that can thus block primary metabolic routes but which do not affect secondary metabolites. 相似文献