全文获取类型
收费全文 | 4204篇 |
免费 | 315篇 |
国内免费 | 2篇 |
专业分类
4521篇 |
出版年
2023年 | 12篇 |
2022年 | 35篇 |
2021年 | 59篇 |
2020年 | 47篇 |
2019年 | 52篇 |
2018年 | 53篇 |
2017年 | 75篇 |
2016年 | 93篇 |
2015年 | 193篇 |
2014年 | 184篇 |
2013年 | 259篇 |
2012年 | 337篇 |
2011年 | 355篇 |
2010年 | 227篇 |
2009年 | 207篇 |
2008年 | 301篇 |
2007年 | 249篇 |
2006年 | 258篇 |
2005年 | 236篇 |
2004年 | 228篇 |
2003年 | 240篇 |
2002年 | 209篇 |
2001年 | 51篇 |
2000年 | 34篇 |
1999年 | 53篇 |
1998年 | 54篇 |
1997年 | 38篇 |
1996年 | 46篇 |
1995年 | 41篇 |
1994年 | 32篇 |
1993年 | 20篇 |
1992年 | 37篇 |
1991年 | 14篇 |
1990年 | 22篇 |
1989年 | 18篇 |
1988年 | 17篇 |
1987年 | 15篇 |
1986年 | 9篇 |
1985年 | 14篇 |
1984年 | 13篇 |
1983年 | 13篇 |
1982年 | 6篇 |
1981年 | 6篇 |
1980年 | 5篇 |
1979年 | 6篇 |
1978年 | 6篇 |
1977年 | 9篇 |
1976年 | 6篇 |
1975年 | 8篇 |
1966年 | 5篇 |
排序方式: 共有4521条查询结果,搜索用时 15 毫秒
101.
Feten Abbassi Zahid Raja Bruno Oury Elodie Gazanion Christophe Piesse Denis Sereno Pierre Nicolas Thierry Foulon Ali Ladram 《Biochimie》2013
Temporins are a family of short antimicrobial peptides (8–17 residues) that mostly show potent activity against Gram-positive bacteria. Herein, we demonstrate that temporin-SHd, a 17-residue peptide with a net charge of +2 (FLPAALAGIGGILGKLFamide), expressed a broad spectrum of antimicrobial activity. This peptide displayed potent antibacterial activities against Gram-negative and Gram-positive bacteria, including multi-drug resistant Staphylococcus aureus strains, as well as antiparasitic activity against promastigote and the intracellular stage (amastigote) of Leishmania infantum, at concentration not toxic for the macrophages. Temporin-SHd that is structured in a non-amphipathic α-helix in anionic membrane-mimetic environments, strongly and selectively perturbs anionic bilayer membranes by interacting with the polar head groups and acyl region of the phospholipids, with formation of regions of two coexisting phases: one phase rich in peptide and the other lipid-rich. The disruption of lipid packing within the bilayer may lead to the formation of transient pores and membrane permeation/disruption once a threshold peptide accumulation is reached. To our knowledge, Temporin-SHd represents the first known 17-residue long temporin expressing such broad spectrum of antimicrobial activity including members of the trypanosomatidae family. Additionally, since only a few shorter members (13 residues) of the temporin family are known to display antileishmanial activity (temporins-TA, -TB and -SHa), SHd is an interesting tool to analyze the antiparasitic mechanism of action of temporins. 相似文献
102.
Thierry M. Brunier Michael G. B. Drew Philip C. H. Mitchell 《Molecular simulation》2013,39(2):143-159
Abstract A method for the parameterisation of molybdenum disulphide is presented which reproduces the crystal structure accurately. The method involves calculating parameters such that there is no net force contribution from any individual term of the potential on any atom. Ideal bond lengths and bond angles are taken from the X-ray crystal structure; stretching and bending force constants are calculated from a combination of spectroscopic data and quantum mechanics calculations, whereby the energy function with bond length or bond angle is calculated and fitted with an harmonic potential. For the non-bonded Lennard-Jones parameters, the dispersion coefficient C was calculated by an interpolation of existing published parameters using a multiple regression and then the crystal energy was minimised with respect to the van der Waals radius r0 using a fixed crystal fragment. These parameters were tested for various models of the hexagonal and rhombohedral forms of MoS2. RMS fits between structures minimised with molecular mechanics and experimental models ranged from 0.006 Å to 0.012 Å. 相似文献
103.
Anna Castaings Jean‐Claude Marchon Dominique Cavagnat Thierry Buffeteau 《Chirality》2013,25(8):480-486
A series of bridled chiroporphyrins (BCP) and their metal complexes were prepared, in which two n‐methylene straps connect adjacent meso substituents by ester linkages. These compounds can exist as four atropisomers (αααα, αβαβ, αααβ, or ααββ) depending on the position of the meso groups relative to the macrocycle (α when above and β when below). We characterized the conformation of these chiral porphyrins and their metal (Zn, Ni, Mn) complexes by vibrational circular dichroism (VCD) associated with ab initio calculations. VCD spectra of the three metalloporphyrins were recorded in CDCl3 and benzene solutions and ab initio calculations of their four atropoisomers were performed at the Density Functional Theory (DFT) level. The bridled chiroporphyrin with the longer straps (9 CH2) and its nickel(II) complex can be isolated as the αβαβ atropisomer in the solid state and were found with the same conformation in CDCl3 and benzene solutions. The bridled chiroporphyrin with the shortest straps (8 CH2) and its zinc(II) complex can be isolated as the αααα atropisomer in the solid state, but in solution they are subject to atropisomeric equilibria, resulting in atropisomer distributions that are strongly solvent‐dependent. Comparison of the experimental VCD spectra with the predicted spectra of the four atropisomers allowed the quantification of these distributions. Finally, the manganese(III) complex also exhibits an atropisomeric equilibria in solution which is slightly solvent‐dependent. Chirality 25:480–486, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
104.
Variations in genomic DNA methylation during the long-term in vitro proliferation of oil palm embryogenic suspension cultures 总被引:1,自引:0,他引:1
Alain Rival Pascal Ilbert Axel Labeyrie Esperanza Torres Sylvie Doulbeau Aline Personne Stéphane Dussert Thierry Beulé Tristan Durand-Gasselin James W. Tregear Estelle Jaligot 《Plant cell reports》2013,32(3):359-368
Key message
The long-term proliferation of embryogenic cell suspensions of oil palm is associated with changes in both genomic methylation rates and embryogenic capacities.Abstract
In the aim of exploring the relationship between epigenetic stability and the long-term in vitro proliferation of plant tissues, we have studied changes in genomic DNA methylation levels in embryogenic suspensions of oil palm (Elaeis guineensis Jacq.). Five embryogenic callus lines were obtained from selected hybrid seeds and then proliferated as suspension cultures. Each clonal line obtained from a single genotype was subdivided into three independent subclonal lines. Once established, cultures proliferated for 12 months and genomic DNA was sampled at 4 months intervals for the estimation of global DNA methylation rates through high performance liquid chromatography (HPLC) quantitation of deoxynucleosides. Our results show that in vitro proliferation induces DNA hypermethylation in a time-dependent fashion. Moreover, this trend is statistically significant in several clonal lines and shared between subclonal lines originating from the same genotype. Interestingly, the only clonal line undergoing loss of genomic methylation in the course of proliferation has been found unable to generate somatic embryos. We discuss the possible implications of genome-wide DNA methylation changes in proliferating cells with a view to the maintenance of genomic and epigenomic stability. 相似文献105.
Audrey Boulamery Gais Kadra Nicolas Simon Thierry Besnard 《Chronobiology international》2013,30(5):961-968
There are no studies indicating a possible modification of imipenem pharmacokinetics related to the hour (i.e., circadian time) of its administration. The aim of this study was to evaluate the influence of different times of intramuscular imipenem administration on its disposition in Wistar AF EOPS rats. Four groups of eight animals were given a single intramuscular injection of 140 mg/kg of imipenem either at 10∶00, 16∶00, 22∶00, or 04∶00 h. Blood samples were collected 0.5, 1, 2, 3, 4, 6, and 8 h after drug injection, and the main pharmacokinetic parameters determined were Cmax, Tmax, elimination half‐life (t1/2), area under the concentration‐versus‐time curve (AUC), total serum clearance (CL/F), and volume of distribution (V/F). Circadian variation of Cmax (49%), Tmax (92%), and AUC (19%) was observed leading to variability of imipenem exposure. Clearance and volume of distribution were modified according to the circadian time of drug injection but did not reach statistical significance. The results suggest that varying the time of administration induces intra‐individual variability. 相似文献
106.
Mylène Desorme Alexandra Montembault Jean-Michel Lucas Cyrille Rochas Thierry Bouet Laurent David 《Carbohydrate polymers》2013
We investigated the spinning of hydroalcoholic chitosan solutions. The dope composition was optimized in order to obtain a continuous alcogel fiber by water evaporation on heating the extruded hydroalcoholic solution. This alcogel fiber was then neutralized in aqueous alkali baths and washed in water to eliminate the residual alcohol and salts before final drying. Depending on the alcohol content in the filament at the neutralization step, on specific alcohol–chitosan interactions and on the nature and concentration of the coagulation base, the process yielded semicrystalline chitosan fibers with different proportions of anhydrous and hydrated allomorphs. Contrarily to the classical annealing method, the formation of mainly anhydrous crystals was obtained without significant molecular weight decrease by neutralizing the polymer in hydrophobic conditions. The control of allomorph content was shown to be related to the hydrophobicity of the solvent (alcohol fraction) at the neutralization step. 相似文献
107.
Maxime Gommeaux Mohamed Barakat Gilles Montagnac Richard Christen François Guyot Thierry Heulin 《Geomicrobiology journal》2013,30(1):76-92
Mineralogy and microbiology of sand from Merzouga (Morocco) were simultaneously characterized, with the purpose of contributing to a better understanding of the geomicrobiology of deserts. In spite of very low measured bacterial biomass, bacterial diversity on each of the five defined mineralogical classes, was found high. An original grain by grain cultivation method enabled to obtain bacterial isolates with an unusually high recovery rate. The results of this study show that the genus Arthrobacter is well adapted to this environment with a preference for grains other than the dominant mineral quartz, and that the genera Chelatococcus and Saccharotrix are strongly attached to the grains. 相似文献
108.
Paulo De Sa Peixoto Guillaume Laurent Thierry Aza?s Gervaise Mosser 《The Journal of biological chemistry》2013,288(11):7528-7535
In vivo, collagen I, the major structural protein in human body, is found assembled into fibrils. In the present work, we study a high concentrated collagen sample in its soluble, fibrillar, and denatured states using one and two dimensional {1H}-13C solid-state NMR spectroscopy. We interpret 13C chemical shift variations in terms of dihedral angle conformation changes. Our data show that fibrillogenesis increases the side chain and backbone structural complexity. Nevertheless, only three to five rotameric equilibria are found for each amino acid residue, indicating a relatively low structural heterogeneity of collagen upon fibrillogenesis. Using side chain statistical data, we calculate equilibrium constants for a great number of amino acid residues. Moreover, based on a 13C quantitative spectrum, we estimate the percentage of residues implicated in each equilibrium. Our data indicate that fibril formation greatly affects hydroxyproline and proline prolyl pucker ring conformation. Finally, we discuss the implication of these structural data and propose a model in which the attractive force of fibrillogenesis comes from a structural reorganization of 10 to 15% of the amino acids. These results allow us to further understand the self-assembling process and fibrillar structure of collagen. 相似文献
109.
Bouchra Ta?b Khalil Bouyakdan Cécile Hryhorczuk Demetra Rodaros Stephanie Fulton Thierry Alquier 《The Journal of biological chemistry》2013,288(52):37216-37229
Hypothalamic controls of energy balance rely on the detection of circulating nutrients such as glucose and long-chain fatty acids (LCFA) by the mediobasal hypothalamus (MBH). LCFA metabolism in the MBH plays a key role in the control of food intake and glucose homeostasis, yet it is not known if glucose regulates LCFA oxidation and esterification in the MBH and, if so, which hypothalamic cell type(s) and intracellular signaling mechanisms are involved. The aim of this study was to determine the impact of glucose on LCFA metabolism, assess the role of AMP-activated Kinase (AMPK), and to establish if changes in LCFA metabolism and its regulation by glucose vary as a function of the kind of LCFA, cell type, and brain region. We show that glucose inhibits palmitate oxidation via AMPK in hypothalamic neuronal cell lines, primary hypothalamic astrocyte cultures, and MBH slices ex vivo but not in cortical astrocytes and slice preparations. In contrast, oleate oxidation was not affected by glucose or AMPK inhibition in MBH slices. In addition, our results show that glucose increases palmitate, but not oleate, esterification into neutral lipids in neurons and MBH slices but not in hypothalamic astrocytes. These findings reveal for the first time the metabolic fate of different LCFA in the MBH, demonstrate AMPK-dependent glucose regulation of LCFA oxidation in both astrocytes and neurons, and establish metabolic coupling of glucose and LCFA as a distinguishing feature of hypothalamic nuclei critical for the control of energy balance. 相似文献
110.
Emilie Widemann Laurence Miesch Rapha?l Lugan Emilie Holder Clément Heinrich Yann Aubert Michel Miesch Franck Pinot Thierry Heitz 《The Journal of biological chemistry》2013,288(44):31701-31714
Jasmonates (JAs) are a class of signaling compounds that mediate complex developmental and adaptative responses in plants. JAs derive from jasmonic acid (JA) through various enzymatic modifications, including conjugation to amino acids or oxidation, yielding an array of derivatives. The main hormonal signal, jasmonoyl-l-isoleucine (JA-Ile), has been found recently to undergo catabolic inactivation by cytochrome P450-mediated oxidation. We characterize here two amidohydrolases, IAR3 and ILL6, that define a second pathway for JA-Ile turnover during the wound response in Arabidopsis leaves. Biochemical and genetic evidence indicates that these two enzymes cleave the JA-Ile signal, but act also on the 12OH-JA-Ile conjugate. We also show that unexpectedly, the abundant accumulation of tuberonic acid (12OH-JA) after wounding originates partly through a sequential pathway involving (i) conjugation of JA to Ile, (ii) oxidation of the JA-Ile conjugate, and (iii) cleavage under the action of the amidohydrolases. The coordinated actions of oxidative and hydrolytic branches in the jasmonate pathway highlight novel mechanisms of JA-Ile hormone turnover and redefine the dynamic metabolic grid of jasmonate conversion in the wound response. 相似文献