全文获取类型
收费全文 | 4847篇 |
免费 | 382篇 |
国内免费 | 1篇 |
专业分类
5230篇 |
出版年
2024年 | 5篇 |
2023年 | 34篇 |
2022年 | 76篇 |
2021年 | 176篇 |
2020年 | 108篇 |
2019年 | 144篇 |
2018年 | 145篇 |
2017年 | 143篇 |
2016年 | 209篇 |
2015年 | 312篇 |
2014年 | 306篇 |
2013年 | 364篇 |
2012年 | 425篇 |
2011年 | 426篇 |
2010年 | 243篇 |
2009年 | 228篇 |
2008年 | 274篇 |
2007年 | 285篇 |
2006年 | 265篇 |
2005年 | 228篇 |
2004年 | 187篇 |
2003年 | 165篇 |
2002年 | 148篇 |
2001年 | 38篇 |
2000年 | 26篇 |
1999年 | 36篇 |
1998年 | 36篇 |
1997年 | 7篇 |
1996年 | 12篇 |
1995年 | 7篇 |
1994年 | 12篇 |
1993年 | 6篇 |
1992年 | 13篇 |
1991年 | 17篇 |
1990年 | 7篇 |
1989年 | 10篇 |
1988年 | 9篇 |
1987年 | 8篇 |
1986年 | 11篇 |
1985年 | 6篇 |
1984年 | 8篇 |
1982年 | 9篇 |
1981年 | 5篇 |
1980年 | 3篇 |
1979年 | 5篇 |
1977年 | 3篇 |
1975年 | 7篇 |
1974年 | 6篇 |
1971年 | 6篇 |
1970年 | 3篇 |
排序方式: 共有5230条查询结果,搜索用时 15 毫秒
151.
Nicola Saino Luca Canova Alessandra Costanzo Diego Rubolini Alexandre Roulin Anders Pape Møller 《Evolutionary biology》2013,40(4):521-531
Eumelanin and pheomelanin are the main endogenous pigments in animals and melanin-based coloration has multiple functions. Melanization is associated with major life-history traits, including immune and stress response, possibly because of pleiotropic effects of genes that control melanogenesis. The net effects on pheo- versus eumelanization and other life-history traits may depend on the antagonistic effects of the genes that trigger the biosynthesis of either melanin form. Covariation between melanin-based pigmentation and fitness traits enforced by pleiotropic genes has major evolutionary implications particularly for socio-sexual communication. However, evidence from non-model organisms in the wild is limited to very few species. Here, we tested the hypothesis that melanin-based coloration of barn swallow (Hirundo rustica) throat and belly feathers covaries with acquired immunity and activation of the hypothalamic–pituitary–adrenal (HPA) axis, as gauged by corticosterone plasma levels. Individuals of both sexes with darker brownish belly feathers had weaker humoral immune response, while darker males had higher circulating corticosterone levels only when parental workload was experimentally reduced. Because color of belly feathers depends on both eu- and pheomelanin, and its darkness decreases with an increase in the concentration of eu- relative to pheomelanin, these results are consistent with our expectation that relatively more eu- than pheomelanized individuals have better immune response and smaller activation of the HPA-axis. Covariation of immune and stress response arose for belly but not throat feather color, suggesting that any function of color as a signal of individual quality or of alternative life-history strategies depends on plumage region. 相似文献
152.
Kristen M. Varney Alexandre M. J. J. Bonvin Marzena Pazgier Jakob Malin Wenbo Yu Eugene Ateh Taiji Oashi Wuyuan Lu Jing Huang Marlies Diepeveen-de Buin Joseph Bryant Eefjan Breukink Alexander D. MacKerell Jr Erik P. H. de Leeuw 《PLoS pathogens》2013,9(11)
We have previously reported on the functional interaction of Lipid II with human alpha-defensins, a class of antimicrobial peptides. Lipid II is an essential precursor for bacterial cell wall biosynthesis and an ideal and validated target for natural antibiotic compounds. Using a combination of structural, functional and in silico analyses, we present here the molecular basis for defensin-Lipid II binding. Based on the complex of Lipid II with Human Neutrophil peptide-1, we could identify and characterize chemically diverse low-molecular weight compounds that mimic the interactions between HNP-1 and Lipid II. Lead compound BAS00127538 was further characterized structurally and functionally; it specifically interacts with the N-acetyl muramic acid moiety and isoprenyl tail of Lipid II, targets cell wall synthesis and was protective in an in vivo model for sepsis. For the first time, we have identified and characterized low molecular weight synthetic compounds that target Lipid II with high specificity and affinity. Optimization of these compounds may allow for their development as novel, next generation therapeutic agents for the treatment of Gram-positive pathogenic infections. 相似文献
153.
154.
The AvrE superfamily: ancestral type III effectors involved in suppression of pathogen‐associated molecular pattern‐triggered immunity 下载免费PDF全文
Alexandre Degrave Sabrina Siamer Tristan Boureau Marie‐Anne Barny 《Molecular Plant Pathology》2015,16(8):899-905
The AvrE superfamily of type III effectors (T3Es) is widespread among type III‐dependent phytobacteria and plays a crucial role during bacterial pathogenesis. Members of the AvrE superfamily are vertically inherited core effectors, indicating an ancestral acquisition of these effectors in bacterial plant pathogens. AvrE‐T3Es contribute significantly to virulence by suppressing pathogen‐associated molecular pattern (PAMP)‐triggered immunity. They inhibit salicylic acid‐mediated plant defences, interfere with vesicular trafficking and promote bacterial growth in planta. AvrE‐T3Es elicit cell death in both host and non‐host plants independent of any known plant resistance protein, suggesting an original interaction with the plant immune system. Recent studies in yeast have indicated that they activate protein phosphatase 2A and inhibit serine palmitoyl transferase, the first enzyme of the sphingolipid biosynthesis pathway. In this review, we describe the current picture that has emerged from studies of the different members of this fascinating large family. 相似文献
155.
Priscila?Innocenti?Justo Juliana?Mo?o?Corrêa Alexandre?Maller Marina?Kimiko?Kadowaki José?Luis?da?Concei??o-Silva Rinaldo?Ferreira?Gandra Rita de?Cássia?Garcia?Sim?oEmail author 《Antonie van Leeuwenhoek》2015,108(4):993-1007
The Caulobacter crescentus (NA1000) xynB5 gene (CCNA_03149) encodes a predicted β-glucosidase-β-xylosidase enzyme that was amplified by polymerase chain reaction; the product was cloned into the blunt ends of the pJet1.2 plasmid. Analysis of the protein sequence indicated the presence of conserved glycosyl hydrolase 3 (GH3), β-glucosidase-related glycosidase (BglX) and fibronectin type III-like domains. After verifying its identity by DNA sequencing, the xynB5 gene was linked to an amino-terminal His-tag using the pTrcHisA vector. A recombinant protein (95 kDa) was successfully overexpressed from the xynB5 gene in E. coli Top 10 and purified using pre-packed nickel-Sepharose columns. The purified protein (BglX-V-Ara) demonstrated multifunctional activities in the presence of different substrates for β-glucosidase (pNPG: p-nitrophenyl-β-D-glucoside) β-xylosidase (pNPX: p-nitrophenyl-β-D-xyloside) and α-arabinosidase (pNPA: p-nitrophenyl-α-L-arabinosidase). BglX-V-Ara presented an optimal pH of 6 for all substrates and optimal temperature of 50 °C for β-glucosidase and α-l-arabinosidase and 60 °C for β-xylosidase. BglX-V-Ara predominantly presented β-glucosidase activity, with the highest affinity for its substrate and catalytic efficiency (Km 0.24 ± 0.0005 mM, Vmax 0.041 ± 0.002 µmol min?1 mg?1 and Kcat/Km 0.27 mM?1 s?1), followed by β-xylosidase (Km 0.64 ± 0.032 mM, Vmax 0.055 ± 0.002 µmol min?1 mg?1 and Kcat/Km 0.14 mM?1s?1) and finally α-l-arabinosidase (Km 1.45 ± 0.05 mM, Vmax 0.091 ± 0.0004 µmol min?1 mg?1 and Kcat/Km 0.1 mM?1 s?1). To date, this is the first report to demonstrate the characterization of a GH3-BglX family member in C. crescentus that may have applications in biotechnological processes (i.e., the simultaneous saccharification process) because the multifunctional enzyme could play an important role in bacterial hemicellulose degradation. 相似文献
156.
Eliane Berrou Alexandre Kauskot Frédéric Adam Amélie Harel Paulette Legendre Cécile Lavenu Bombled Chantal Rothschild Nicolas Prevost Olivier D. Christophe Peter J. Lenting Cécile V. Denis Jean-Philippe Rosa Marijke Bryckaert 《PloS one》2015,10(12)
Thrombocytopenia and increased platelet clearance observed in von Willebrand disease-type 2B (VWD-2B) may be explained by platelet apoptosis triggered by the constitutive binding of VWF to its receptor, glycoprotein Ib (GPIb). Apoptosis was assessed in platelets from two patients with a severe VWD-2B mutation VWF/p.V1316M and from mice transiently expressing VWF/p.V1316M. We now report that the VWD-2B mutation VWF/p.V1316M which binds spontaneously to its receptor GPIbα does not induce apoptosis. In 2 unrelated patients (P1 and P2) exhibiting different VWF plasma levels (70% and 36%, respectively, compared with normal pooled human plasma given as 100%), inner transmembrane depolarization of mitochondria, characteristic of apoptotic events was undetectable in platelets, whether washed or in whole blood. No or a moderate phosphatidyl serine (PS) exposure as measured by annexin-V staining was observed for P1 and P2, respectively. Expression of pro-apoptotic proteins Bak and Bax, and caspase-3 activity were similar to control platelets. In the VWD-2B mouse model expressing high levels of mVWF/p.V1316M (423%), similar to what is found in inflammatory pathologies, no significant difference was observed between mice expressing mVWF/WT and mVWF/p.V1316M. These results strongly argue against apoptosis as a mechanism for the thrombocytopenia of severe VWD-2B exhibiting the VWF/p.V1316M mutation. 相似文献
157.
Qiao Huang Kostiantyn Turcheniuk Xiaolei Ren Alexandre Magasinski Daniel Gordon Nasr Bensalah Gleb Yushin 《Liver Transplantation》2019,9(17)
As an alternative to commercial Ni‐ and Co‐based intercalation‐type cathode materials, conversion‐type metal fluoride (MFx) cathodes are attracting more interest due to their promises to increase cell‐level energy density when coupled with lithium (Li) or silicon (Si)‐based anodes. Among metal fluorides, iron fluorides (FeF2 and FeF3) are regarded as some of the most promising candidates due to their high capacity, moderately high potential and the very low cost of Fe. In this study, the impacts of electrolyte composition on the performance and stability of nanostructured FeF2 cathodes are systematically investigated. Dramatic impacts of Li salt composition, Li salt concentration, solvent composition, and cycling potential range on the cathode's most critical performance parameters—stability, capacity, rate, and voltage hysteresis are discovered. In contrast to previous beliefs, it is observed that even if the Fe2+ cation dissolution could be avoided, the dissolution of F? anions may still negatively affect cathode performance. Formation of the more favorable cathode solid electrolyte interface (CEI) is found to minimize both processes. 相似文献
158.
Laura Estelle Yêyinou Loko Azize Orobiyi Paterne Agre Alexandre Dansi Manuele Tamò Yves Roisin 《Journal of ethnobiology and ethnomedicine》2017,13(1):64
Background
Although termites are considered as agricultural pests, they play an important role in maintaining the ecosystem. Therefore, it matters to investigate the farmers’ perception of the impacts of the termites on the agriculture and their indigenous utilization.Methods
A semi-structured questionnaire was used to interview 94 farmers through 10 villages of Atacora department, in the northwestern region of Benin, to obtain information for the development of successful strategies of termite management and conservation. Their perceptions on the importance and management of termites along with the indigenous nomenclature and utilization of termite mounds were assessed. Termite species identified by farmers were collected and preserved in 80% alcohol for identification.Results
Eight crops were identified by farmers as susceptible to termites with maize, sorghum, and yam as being the most susceptible. According to farmers, the susceptibility to termites of these crops is due to their high-water content and sweet taste. A total of 27 vernacular names of termites were recorded corresponding to 10 species, Amitermes evuncifer, Macrotermes subhyalinus, and Trinervitermes oeconomus being the most damaging termite species. All the names given to termite species had a meaning. The drought was identified by farmers as the main factor favouring termite attacks. Demolition of termite mounds in the fields was the most commonly reported control method. Salt and other pesticides were commonly used by farmers to protect stored farm products. The lack of effective control methods is the main constraint for termite management. In northwestern Benin, farmers reported different purpose utilizations of termite mounds and termites.Conclusions
The study has shown that farmers perceived termites as pests of several agricultural crops and apply various indigenous control practices whose efficiency need to be verified. Utilization of termites and termite mound soil as food and medicinal resources underlines the need for a more focused approach to termite control for the conservation of non-pest termite species. The sensitization of farmers on the importance of termites as well as the development of an integrated control method to combat termite pests proved necessary.159.
160.
Bezerra EH Rocha BA Nagano CS Bezerra Gde A Moura TR Bezerra MJ Benevides RG Sampaio AH Assreuy AM Delatorre P Cavada BS 《Biochemical and biophysical research communications》2011,(4):566-570
Diocleinae lectins are highly homologous in their primary structure which features metal binding sites and a carbohydrate recognition domain (CRD). Differences in the biological activity of legume lectins have been widely investigated using hemagglutination inhibition assays, isothermal titration microcalorimetry and co-crystallization with mono- and oligosaccharides. Here we report a new lectin crystal structure (ConBr) extracted from seeds of Canavalia brasiliensis, predict dimannoside binding by docking, identify the α-aminobutyric acid (Abu) binding pocket and compare the CRD of ConBr to that of homologous lectins. Based on the hypothesis that the carbohydrate affinity of lectins depends on CRD configuration, the relationship between tridimensional structure and endothelial NO synthase activation was used to clarify differences in biological activity. Our study established a correlation between the position of CRD amino acid side chains and the stimulation of NO release from endothelium. 相似文献