全文获取类型
收费全文 | 553篇 |
免费 | 32篇 |
国内免费 | 4篇 |
出版年
2023年 | 4篇 |
2022年 | 18篇 |
2021年 | 17篇 |
2020年 | 15篇 |
2019年 | 20篇 |
2018年 | 27篇 |
2017年 | 16篇 |
2016年 | 34篇 |
2015年 | 41篇 |
2014年 | 39篇 |
2013年 | 26篇 |
2012年 | 38篇 |
2011年 | 39篇 |
2010年 | 25篇 |
2009年 | 20篇 |
2008年 | 30篇 |
2007年 | 27篇 |
2006年 | 18篇 |
2005年 | 19篇 |
2004年 | 17篇 |
2003年 | 16篇 |
2002年 | 11篇 |
2001年 | 9篇 |
2000年 | 7篇 |
1999年 | 3篇 |
1998年 | 5篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1983年 | 8篇 |
1981年 | 1篇 |
1978年 | 4篇 |
1977年 | 1篇 |
1975年 | 2篇 |
1973年 | 3篇 |
1972年 | 3篇 |
1970年 | 1篇 |
1966年 | 2篇 |
排序方式: 共有589条查询结果,搜索用时 31 毫秒
61.
Plasmepsin (PM) II is one of four enzymes in the food vacuole of Plasmodium falciparum. It has become an attractive target for combating malaria through research regarding its importance in the P. falciparum metabolism and life cycle, making it the target of choice for structure-based drug design. This paper reports the results of hybrid quantum mechanics / molecular mechanics (QM/MM) molecular dynamics (MD) simulations employed to study the details of the interactions established between PM II and N-(3-{(2-benzo[1, 3]dioxol-5-yl-ethyl)[3-(1-methyl-3-oxo-1,3-dihydro-isoindol-2-yl) propionyl]-amino}-1-benzyl-2-(hydroxyl-propyl)-4-benzyloxy-3,5dimethoxy-benzamide (EH58), a well-known potent inhibitor for this enzyme. Electrostatic binding free energy and energy terms decomposition have been computed for PM II complexed with the EH58 inhibitor. The results reveal that there is a strong interaction between Asp34, Val78, Ser79, Tyr192 and Asp214 residues and the EH58 inhibitor. In addition, we have computed the potential of the mean force (PMF) profile in order to assign the protonation state of the two catalytic aspartates in PM II-EH58 complex. The results indicate that the protonation of Asp214 favors a stable active site structure, which is consistent with our electrostatic binding free energy calculation and with previous published works. 相似文献
62.
de Lira FA Farias Mde S de Figueiredo AF Gil Fdos S dos Santos MA Malheiros BV Ferreira JE Pinheiro JC Treu-Filho O Kondo RT 《Journal of molecular modeling》2011,17(7):1621-1624
In a previous article, we used Hartree-Fock (HF) theory to study the piezoelectricity in BaTiO3. In this paper, we applied the Douglas-Kroll-Hess second order scalar relativistic method to investigate the possible piezoelectric
properties in the perovskite YFeO3 structure, which has not yet been studied experimentally. The 30s20p13d and 31s21p17d Gaussian basis sets for the Fe (5D) and Y (2D) atoms, respectively, were built with the Generator Coordinate HF method. After contraction to [13s7p5d] and [13s8p7d],
in combination with the 20s14p/6s4p basis set for the O (3P) atom from literature, they had their quality evaluated using calculations of the total and the orbital energies for the
2FeO+1 and 1YO+1 fragments. The dipole moment, the total energy, and the total atomic charges in YFeO3 in Cs space group were calculated. The results and the analysis lead us to believe that the perovskite YFeO3 does not present piezoelectric properties. 相似文献
63.
Roseane Borner Jo?o Bento-Torres Diego RV Souza Danyelle B Sadala Nonata Trevia José Augusto Farias Nara Lins Aline Passos Amanda Quintairos José Ant?nio Diniz Victor Hugh Perry Pedro Fernando Vasconcelos Colm Cunningham Cristovam W Pican?o-Diniz 《朊病毒》2011,5(3):215-227
Behavioral and neuropathological changes have been widely investigated in murine prion disease but stereological based unbiased estimates of key neuropathological features have not been carried out. After injections of ME7 infected (ME7) or normal brain homogenates (NBH) into dorsal CA1 of albino Swiss mice and C57BL6, we assessed behavioral changes on hippocampal-dependent tasks. We also estimated by optical fractionator at 15 and 18 weeks post-injections (w.p.i.) the total number of neurons, reactive astrocytes, activated microglia and perineuronal nets (PN) in the polymorphic layer of dentate gyrus (PolDG), CA1 and septum in albino Swiss mice. On average, early behavioral changes in albino Swiss mice start four weeks later than in C57BL6. Cluster and discriminant analysis of behavioral data in albino Swiss mice revealed that four of nine subjects start to change their behavior at 12 w.p.i. and reach terminal stage at 22 w.p.i and the remaining subjects start at 22 w.p.i. and reach terminal stage at 26 w.p.i. Biotinylated dextran-amine BDA-tracer experiments in mossy fiber pathway confirmed axonal degeneration and stereological data showed that early astrocytosis, microgliosis and reduction in the perineuronal nets are independent of a change in the number of neuronal cell bodies. Statistical analysis revealed that the septal region had greater levels of neuroinflammation and extracellular matrix damage than CA1. This stereological and multivariate analysis at early stages of disease in an outbred model of prion disease provided new insights connecting behavioral changes and neuroinflammation and seems to be important to understand the mechanisms of prion disease progression.Key words: prion disease, optical fractionator, neuropathology, behavioral changes, albino Swiss mice 相似文献
64.
Molecular Ecology Resources Primer Development Consortium Agata K Alasaad S Almeida-Val VM Alvarez-Dios JA Barbisan F Beadell JS Beltrán JF Benítez M Bino G Bleay C Bloor P Bohlmann J Booth W Boscari E Caccone A Campos T Carvalho BM Climaco GT Clobert J Congiu L Cowger C Dias G Doadrio I Farias IP Ferrand N Freitas PD Fusco G Galetti PM Gallardo-Escárate C Gaunt MW Ocampo ZG Gonçalves H Gonzalez EG Haye P Honnay O Hyseni C Jacquemyn H Jowers MJ Kakezawa A Kawaguchi E Keeling CI Kwan YS 《Molecular ecology resources》2011,11(3):586-589
This article documents the addition of 238 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Alytes dickhilleni, Arapaima gigas, Austropotamobius italicus, Blumeria graminis f. sp. tritici, Cobitis lutheri, Dendroctonus ponderosae, Glossina morsitans morsitans, Haplophilus subterraneus, Kirengeshoma palmata, Lysimachia japonica, Macrolophus pygmaeus, Microtus cabrerae, Mytilus galloprovincialis, Pallisentis (Neosentis) celatus, Pulmonaria officinalis, Salminus franciscanus, Thais chocolata and Zootoca vivipara. These loci were cross-tested on the following species: Acanthina monodon, Alytes cisternasii, Alytes maurus, Alytes muletensis, Alytes obstetricans almogavarii, Alytes obstetricans boscai, Alytes obstetricans obstetricans, Alytes obstetricans pertinax, Cambarellus montezumae, Cambarellus zempoalensis, Chorus giganteus, Cobitis tetralineata, Glossina fuscipes fuscipes, Glossina pallidipes, Lysimachia japonica var. japonica, Lysimachia japonica var. minutissima, Orconectes virilis, Pacifastacus leniusculus, Procambarus clarkii, Salminus brasiliensis and Salminus hilarii. 相似文献
65.
66.
Estevam FR Augusto SF Rodrigues SA Pinheiro MR Monteiro AF 《Cancer immunology, immunotherapy : CII》2005,54(7):671-676
Tumor necrosis factor alpha (TNF-) is a cytokine that acts as an important mediator of the apoptotic process that also demonstrates selective citotoxicity against malignant breast tumor cells. In the present study, the presence of apoptotic tumor cells and the synthesis of TNF- by inflammatory cells were investigated in tissue samples from grade III invasive breast cancer with long-term follow-up. In situ detection of tumor apoptotic cells was investigated by direct immuno-peroxidase of digoxigenin-labeled genomic DNA. The production of TNF- and tumor cell proliferation were investigated by immunohistochemical procedures. Our data demonstrated that patients with a clinical history of cancer recurrence and metastasis presented a lower number of cancerous apoptotic cells, higher tumor proliferation rates, and lower TNF- expression rates by inflammatory cells than what is observed among patients diagnosed with the same histopathological breast cancer type but in the absence of tumor recurrence and metastasis. 相似文献
67.
Gorman MW Farias M Richmond KN Tune JD Feigl EO 《American journal of physiology. Heart and circulatory physiology》2005,288(4):H1937-H1942
It has been proposed that alpha-adrenoceptor vasoconstriction in coronary resistance vessels results not from alpha-adrenoceptors on coronary smooth muscle but from alpha-adrenoceptors on cardiac myocytes that stimulate endothelin (ET) release. The present experiments tested the hypothesis that the alpha-adrenoceptor-mediated coronary vasoconstriction that normally occurs during exercise is due to endothelin. In conscious dogs (n = 10), the endothelin ET(A)/ET(B) receptor antagonist tezosentan (1 mg/kg iv) increased coronary venous oxygen tension at rest but not during treadmill exercise. This result indicates that basal endothelin levels produce a coronary vasoconstriction at rest that is not observed during the coronary vasodilation during exercise. In contrast, the alpha-adrenoceptor antagonist phentolamine increased coronary venous oxygen tension during exercise but not at rest. The difference between the endothelin blockade and alpha-adrenoceptor blockade results indicates that alpha-adrenoceptor coronary vasoconstriction during exercise is not due to endothelin. However, in anesthetized dogs, bolus intracoronary injections of the alpha-adrenoceptor agonist phenylephrine produced reductions in coronary blood flow that were partially antagonized by endothelin receptor blockade with tezosentan. These results are best explained if alpha-adrenoceptor-induced endothelin release requires high pharmacological concentrations of catecholamines that are not reached during exercise. 相似文献
68.
Cantanhede AM Da Silva VM Farias IP Hrbek T Lazzarini SM Alves-Gomes J 《Molecular ecology》2005,14(2):401-413
We used mitochondrial DNA control region sequences to examine phylogeography and population differentiation of the endangered Amazonian manatee Trichechus inunguis. We observe lack of molecular differentiation among localities and we find weak association between geographical and genetic distances. However, nested clade analysis supports restricted gene flow and/or dispersal with some long-distance dispersal. Although this species has a history of extensive hunting, genetic diversity and effective population sizes are relatively high when compared to the West Indian manatee Trichechus manatus. Patterns of mtDNA haplotype diversity in T. inunguis suggest a genetic disequilibrium most likely explained by demographic expansion resulting from secession of hunting and enforcement of conservation and protective measures. Phylogenetic analysis of T. manatus and T. inunguis haplotypes suggests that T. inunguis is nested within T. manatus, effectively making T. manatus a paraphyletic entity. Paraphyly of T. manatus and recent divergence times of T. inunguis and the three main T. manatus lineages suggest a possible need for a taxonomic re-evaluation of the western Atlantic Trichechus. 相似文献
69.
Ribeiro DT Farias LP de Almeida JD Kashiwabara PM Ribeiro AF Silva-Filho MC Menck CF Van Sluys MA 《Journal of experimental botany》2005,56(417):1797-1804
The Arabidopsis thaliana THI1 protein is involved in thiamine biosynthesis and is targeted to both chloroplasts and mitochondria by N-terminal control regions. To investigate thi1 expression, a series of thi1 promoter deletions were fused to the beta-glucuronidase (GUS) reporter gene. Transgenic plants were generated and expression patterns obtained under different environmental conditions. The results show that expression derived from the thi1 promoter is detected early on during development and continues throughout the plant's life cycle. High levels of GUS expression are observed in both shoots and roots during vegetative growth although, in roots, expression is restricted to the vascular system. Deletion analysis of the thi1 promoter region identified a region that is responsive to light. The smallest fragment (designated Pthi322) encompasses 306 bp and possesses all the essential signals for tissue specificity, as well as responsiveness to stress conditions such as sugar deprivation, high salinity, and hypoxia. 相似文献
70.
Del Vecchio P Graziano G Granata V Farias T Barone G Mandrich L Rossi M Manco G 《Biochemistry》2004,43(46):14637-14643
The stability of acetyl-esterase, Aes, from Escherichia coli against the denaturing action of urea and guanidine hydrochloride, GuHCl, has been investigated by means of circular dichroism and fluorescence measurements. The urea-induced unfolding curves show a single inflection point at 6.2 M urea, whereas the GuHCl-induced curves show two inflection points at 1.4 and 3.1 M GuHCl. The unfolding process is reversible with both urea and GuHCl. These results, together with similar experimental data on the mutant form V20D-Aes, suggest the presence of two domains in the Aes structure, which unfold more or less independently depending on the denaturant used. This is also supported by a 3D model obtained by homology modeling using the structure of brefeldine as a template. The effect of NaCl on the urea-induced unfolding curves of the enzyme has also been investigated. 相似文献