全文获取类型
收费全文 | 2405篇 |
免费 | 171篇 |
专业分类
2576篇 |
出版年
2023年 | 22篇 |
2022年 | 35篇 |
2021年 | 68篇 |
2020年 | 54篇 |
2019年 | 62篇 |
2018年 | 76篇 |
2017年 | 84篇 |
2016年 | 114篇 |
2015年 | 141篇 |
2014年 | 153篇 |
2013年 | 172篇 |
2012年 | 184篇 |
2011年 | 194篇 |
2010年 | 106篇 |
2009年 | 96篇 |
2008年 | 109篇 |
2007年 | 112篇 |
2006年 | 105篇 |
2005年 | 82篇 |
2004年 | 82篇 |
2003年 | 72篇 |
2002年 | 60篇 |
2001年 | 51篇 |
2000年 | 68篇 |
1999年 | 45篇 |
1998年 | 15篇 |
1997年 | 15篇 |
1996年 | 10篇 |
1995年 | 15篇 |
1994年 | 12篇 |
1993年 | 10篇 |
1992年 | 13篇 |
1991年 | 11篇 |
1990年 | 11篇 |
1989年 | 13篇 |
1988年 | 8篇 |
1987年 | 9篇 |
1986年 | 6篇 |
1984年 | 4篇 |
1983年 | 7篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1980年 | 4篇 |
1979年 | 6篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1974年 | 7篇 |
1973年 | 12篇 |
1972年 | 3篇 |
1970年 | 4篇 |
排序方式: 共有2576条查询结果,搜索用时 0 毫秒
991.
992.
993.
Claudia Terencio Agostinho Pires Mislaine Adriana Brenzan Regiane Bertin de Lima Scodro Diógenes Aparício Garcia Cortez Luciana Dias Ghiraldi Lopes Vera Lucia Dias Siqueira Rosilene Fressatti Cardoso 《Memórias do Instituto Oswaldo Cruz》2014,109(3):324-329
We evaluated the in vitro anti-Mycobacterium tuberculosis activity and the
cytotoxicity of dichloromethane extract and pure compounds from the leaves of
Calophyllum brasiliense. Purification of the dichloromethane extract yielded the pure
compounds (-) mammea A/BB (1), (-) mammea B/BB (2) and amentoflavone (3). The
compound structures were elucidated on the basis of spectroscopic and spectrometric
data. The contents of bioactive compounds in the extracts were quantified using high
performance liquid chromatography coupled to an ultraviolet detector. The anti-M.
tuberculosis activity of the extracts and the pure compounds was evaluated using a
resazurin microtitre assay plate. The cytotoxicity assay was performed in J774G.8
macrophages using the 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide
colourimetric method. The quantification of the dichloromethane extract showed (1)
and (2) at concentrations of 31.86 ± 2.6 and 8.24 ± 1.1 µg/mg of extract,
respectively. The dichloromethane and aqueous extracts showed anti-M. tuberculosis
H37Rv activity of 62.5 and 125 µg/mL, respectively. Coumarins (1) and (2) showed
minimal inhibitory concentration ranges of 31.2 and 62.5 µg/mL against M.
tuberculosis H37Rv and clinical isolates. Compound (3) showed no activity against M.
tuberculosis H37Rv. The selectivity index ranged from 0.59-1.06. We report the
activity of the extracts and coumarins from the leaves of C. brasiliense against M.
tuberculosis. 相似文献
994.
Lopes DH Chapeaurouge A Manderson GA Johansson JS Ferreira ST 《The Journal of biological chemistry》2004,279(12):10991-10996
Because of their limited size and complexity, de novo designed proteins are particularly useful for the detailed investigation of folding thermodynamics and mechanisms. Here, we describe how subtle changes in the hydrophobic core of a model three-helix bundle protein (GM-0) alter its folding energetics. To explore the folding tolerance of GM-0 toward amino acid sequence variability, two mutant proteins (GM-1 and GM-2) were generated. In the mutants, cavities were created in the hydrophobic core of the protein by either singly (GM-1; L35A variant) or doubly (GM-2; L35A/I39A variant) replacing large hydrophobic side chains by smaller Ala residues. The folding of GM-0 is characterized by two partially folded intermediate states exhibiting characteristics of molten globules, as evidenced by pressure-unfolding and pressure-assisted cold denaturation experiments. In contrast, the folding energetics of both mutants, GM-1 and GM-2, exhibit only one folding intermediate. Our results support the view that simple but biologically important folding motifs such as the three-helix bundle can reveal complex folding plasticity, and they point to the role of hydrophobic packing as a determinant of the overall stability and folding thermodynamic of the helix bundle. 相似文献
995.
Carlos Eduardo Almeida Paula L. Marcet Marcia Gumiel Daniela Maeda Takiya Margareth Cardozo‐de‐Almeida Raquel S Pacheco Catarina Macedo Lopes Ellen M. Dotson Jane Costa 《Journal of vector ecology》2009,34(2):164-173
Triatoma carcavalloi is considered a rare Chagas disease vector often collected inside domiciles in Rio Grande do Sul State. In this Brazilian state, T. carcavalloi has been collected in the same ecotope (rock piles) with two other species (T. rubrovaria and T. circummaculata), with which it also shares morphological characteristics. Previous morphological studies placed T. carcavalloi in the same species complex (“infestans complex”) and subcomplex (“rubrovaria subcomplex”) as T. rubrovaria, whereas T. circummaculata was placed in the “circummaculata complex.” The phylogeny of a group composed of 16 species of triatomines was revaluated with the inclusion of T. carcavalloi by Bayesian analysis using mtDNA sequences of subunits 12S and 16S of the ribosomal RNA, and the cytochrome oxidase I (COI) genes. The phenotypic relationship among T. carcavalloi and related triatomines was also inferred from morphometrics. Phylogenetic results indicate that T. carcavalloi is a sister species of T. rubrovaria, and both were recovered as closely related to T. circummaculata. Morphometric studies confirmed the closeness among T. carcavalloi, T. rubrovaria, and T. circummaculata, prompting the placement of the latter species in the “infestans complex” and “rubrovaria subcomplex.” 相似文献
996.
Sousa EH Pontes DL Diógenes IC Lopes LG Oliveira JS Basso LA Santos DS Moreira IS 《Journal of inorganic biochemistry》2005,99(2):368-375
The mechanism of activation thioamide-pyridine anti-tuberculosis prodrugs is poorly described in the literature. It has recently been shown that ethionamide, an important component of second-line therapy for the treatment of multi-drug-resistant tuberculosis, is activated through an enzymatic electron transfer (ET) reaction. In an attempt to shed light on the activation of thioamide drugs, we have mimicked a redox process involving the thionicotinamide (thio) ligand, investigating its reactivity through coordination to the redox reversible [Fe(III/II)(CN)(5)(H(2)O)](2-/3-) metal center. The reaction of the Fe(III) complex with thionicotinamide leads to the ligand conversion to the 3-cyanopyridine species coordinated to a Fe(II) metal center. The rate constant, k(et)=10 s(-1), was determined for this intra-molecular ET reaction. A kinetic study for the cross-reaction of thionicotinamide and [Fe(CN)(6)](3-) was also carried out. The oxidation of thionicotinamide by [Fe(CN)(6)](3-) leads to formation of mainly 3-cyanopyridine and [Fe(CN)(6)](4-) with a k(et)=(5.38+/-0.03) M(-1)s(-1) at 25 degrees C, pH 12.0. The rate of this reaction is strongly dependent on pH due to an acid-base equilibrium related to the deprotonation of the R-SH functional group of the imidothiol form of thionicotinamide. The kinetic results reinforced the assignment of an intra-molecular mechanism for the ET reaction of [Fe(III)(CN)(5)(H(2)O)](2-) and the thioamide ligand. These results can be valuable for the design of new thiocarbonyl-containing drugs against resistant strains of Mycobacterium tuberculosis by a self-activating mechanism. 相似文献
997.
Carlos Novo Tiago M. Martins Sofia Prata ngela Lopes Ana Armada 《International journal of biological macromolecules》2009,45(4):399-406
Malaria remains one of the major human parasitic diseases, particularly in subtropical regions. Most of the fatal cases are caused by Plasmodium falciparum. The rodent parasite Plasmodium chabaudi has been the model of choice in research due to its similarities to human malaria, including developmental cycle, preferential invasion of mature erythrocytes, synchrony of asexual development, antigenic variation, gene sinteny as well as similar resistance mechanisms. Protein disulfide isomerase (PDI) is an essential catalyst of the endoplasmic reticulum in different biological systems with folding and chaperone activities. Most of the proteins exported by parasites have to pass through the endoplasmic reticulum before reaching their final destination and their correct folding is critical for parasite survival. PDI constitutes a potential target for the development of alternative therapy strategies based on the inhibition of folding and chaperoning of exported proteins. We here describe the sequencing of the gene coding for the PDI from P. chabaudi and analyse the relationship to its counterpart enzymes, particularly with the PDI from other Plasmodium species. The model constructed, based on the recent model deduced from the crystallographic structure 2B5E, was compared with the previous theoretical model for the whole PDI molecule constructed by threading. A recombinant PDI from P. chabaudi was also produced and used as an antigen for monoclonal antibody production for application in PDI immunolocalization. 相似文献
998.
999.
Sandra Beleza Joana Campos Jailson Lopes Isabel Inês Araújo Ana Hoppfer Almada António Correia e Silva Esteban J. Parra Jorge Rocha 《PloS one》2012,7(11)
Recently admixed populations offer unique opportunities for studying human history and for elucidating the genetic basis of complex traits that differ in prevalence between human populations. Historical records, classical protein markers, and preliminary genetic data indicate that the Cape Verde islands in West Africa are highly admixed and primarily descended from European males and African females. However, little is known about the variation in admixture levels, admixture dynamics and genetic diversity across the islands, or about the potential of Cape Verde for admixture mapping studies. We have performed a detailed analysis of phenotypic and genetic variation in Cape Verde based on objective skin color measurements, socio-economic status (SES) evaluations and data for 50 autosomal, 34 X-chromosome, and 21 non-recombinant Y-chromosome (NRY) markers in 845 individuals from six islands of the archipelago. We find extensive genetic admixture between European and African ancestral populations (mean West African ancestry = 0.57, sd = 0.08), with individual African ancestry proportions varying considerably among the islands. African ancestry proportions calculated with X and Y-chromosome markers confirm that the pattern of admixture has been sex-biased. The high-resolution NRY-STRs reveal additional patterns of variation among the islands that are most consistent with differentiation after admixture. The differences in the autosomal admixture proportions are clearly evident in the skin color distribution across the islands (Pearson r = 0.54, P-value<2e–16). Despite this strong correlation, there are significant interactions between SES and skin color that are independent of the relationship between skin color and genetic ancestry. The observed distributions of admixture, genetic variation and skin color and the relationship of skin color with SES relate to historical and social events taking place during the settlement history of Cape Verde, and have implications for the design of association studies using this population. 相似文献
1000.
Diego Lopes Mendes Barretti Flávio de Castro Magalh?es Tiago Fernandes Everton Crivoi do Carmo Kaleizu Teodoro Rosa Maria Claudia Irigoyen Carlos Eduardo Negr?o Edilamar Menezes Oliveira 《PloS one》2012,7(10)