全文获取类型
收费全文 | 4772篇 |
免费 | 283篇 |
出版年
2023年 | 52篇 |
2022年 | 48篇 |
2021年 | 142篇 |
2020年 | 107篇 |
2019年 | 146篇 |
2018年 | 178篇 |
2017年 | 135篇 |
2016年 | 187篇 |
2015年 | 300篇 |
2014年 | 297篇 |
2013年 | 363篇 |
2012年 | 390篇 |
2011年 | 371篇 |
2010年 | 211篇 |
2009年 | 209篇 |
2008年 | 238篇 |
2007年 | 228篇 |
2006年 | 235篇 |
2005年 | 168篇 |
2004年 | 140篇 |
2003年 | 136篇 |
2002年 | 117篇 |
2001年 | 89篇 |
2000年 | 85篇 |
1999年 | 57篇 |
1998年 | 40篇 |
1997年 | 24篇 |
1996年 | 21篇 |
1995年 | 19篇 |
1994年 | 17篇 |
1993年 | 13篇 |
1992年 | 27篇 |
1991年 | 24篇 |
1990年 | 15篇 |
1989年 | 22篇 |
1988年 | 12篇 |
1987年 | 15篇 |
1986年 | 20篇 |
1985年 | 15篇 |
1984年 | 12篇 |
1983年 | 10篇 |
1982年 | 9篇 |
1981年 | 14篇 |
1979年 | 15篇 |
1978年 | 9篇 |
1976年 | 6篇 |
1975年 | 8篇 |
1974年 | 10篇 |
1973年 | 7篇 |
1968年 | 5篇 |
排序方式: 共有5055条查询结果,搜索用时 6 毫秒
1.
2.
3.
4.
Claudiane V. Almeida Caio F.R. de Oliveira Edson L. dos Santos Helder F. dos Santos Edson C. Júnior Reinaldo Marchetto Leticia A. da Cruz Alda Maria T. Ferreira Valdirene M. Gomes Gabriel B. Taveira Bruna O. Costa Octávio L. Franco Marlon H. Cardoso Maria Lígia R. Macedo 《Biochimica et Biophysica Acta (BBA)/General Subjects》2021,1865(9):129937
BackgroundAntimicrobial peptides (AMPs) are molecules with potential application for the treatment of microorganism infections. We, herein, describe the structure, activity, and mechanism of action of RQ18, an α-helical AMP that displays antimicrobial activity against Gram-positive and Gram-negative bacteria, and yeasts from the Candida genus.MethodsA physicochemical-guided design assisted by computer tools was used to obtain our lead peptide candidate, named RQ18. This peptide was assayed against Gram-positive and Gram-negative bacteria, yeasts, and mammalian cells to determine its selectivity index. The secondary structure and the mechanism of action of RQ18 were investigated using circular dichroism, large unilamellar vesicles, and molecular dynamic simulations.ResultsRQ18 was not cytotoxic to human lung fibroblasts, peripheral blood mononuclear cells, red blood cells, or Vero cells at MIC values, exhibiting a high selectivity index. Circular dichroism analysis and molecular dynamic simulations revealed that RQ18 presents varying structural profiles in aqueous solution, TFE/water mixtures, SDS micelles, and lipid bilayers. The peptide was virtually unable to release carboxyfluorescein from large unilamellar vesicles composed of POPC/cholesterol, model that mimics the eukaryotic membrane, indicating that vesicles' net charges and the presence of cholesterol may be related with RQ18 selectivity for bacterial and fungal cell surfaces.ConclusionsRQ18 was characterized as a membrane-active peptide with dual antibacterial and antifungal activities, without compromising mammalian cells viability, thus reinforcing its therapeutic application.General significanceThese results provide further insight into the complex process of AMPs interaction with biological membranes, in special with systems that mimic prokaryotic and eukaryotic cell surfaces. 相似文献
5.
6.
Margarida A. Ferreira M.Aurea Cruz Costa A.Correia Alves M.Helena Lopes 《Phytochemistry》1973,12(2):433-435
7-MethyljugIone, 8,8′-dihydroxy-4,4′-dimethoxy-6,6′-dimethyl-2,2′-binaphthyl-1,1′-quinone, 2-methylnaphthazarin, mamegakinone and euclein have been isolated from Euclea pseudebenus. Euclein is the 3,6′-dimer of 7-methyljuglone. 相似文献
7.
8.
Antonio Hernandes Chaves Neto Karla Cristiana Queiroz Renato Milani Edgar Julian Paredes‐Gamero Giselle Zenker Justo Maikel P. Peppelenbosch Carmen Veríssima Ferreira 《Journal of cellular biochemistry》2011,112(1):71-77
Despite numerous reports on the ability of ascorbic acid and β‐glycerophosphate (AA/β‐GP) to induce osteoblast differentiation, little is known about the molecular mechanisms involved in this phenomenon. In this work, we used a peptide array containing specific consensus sequences (potential substrates) for protein kinases and traditional biochemical techniques to examine the signaling pathways modulated during AA/β‐GP‐induced osteoblast differentiation. The kinomic profile obtained after 7 days of treatment with AA/β‐GP identified 18 kinase substrates with significantly enhanced or reduced phosphorylation. Peptide substrates for Akt, PI3K, PKC, BCR, ABL, PRKG1, PAK1, PAK2, ERK1, ERBB2, and SYK showed a considerable reduction in phosphorylation, whereas enhanced phosphorylation was observed in substrates for CHKB, CHKA, PKA, FAK, ATM, PKA, and VEGFR‐1. These findings confirm the potential usefulness of peptide microarrays for identifying kinases known to be involved in bone development in vivo and in vitro and show that this technique can be used to investigate kinases whose function in osteoblastic differentiation is poorly understood. J. Cell. Biochem. 112: 71–77, 2011. © 2010 Wiley‐Liss, Inc. 相似文献
9.
Mitracarpus longicalyx is here described and illustrated from sandy areas of the caatingas of northeastern Brazil. The new species is similar toM. hirtus andM. megapotamicus. 相似文献
10.
Y Revilla A Ferreira M L Villar A Bootello P Gonzalez-Porqué 《The Journal of biological chemistry》1986,261(14):6486-6491
The effect of temperature, urea, guanidine HCl, ionic and nonionic detergents, organic solvents, chaotropic salts, pH, and divalent cations has been investigated on purified human histocompatibility antigens solubilized by papain (HLApap) or solubilized by sodium cholate (HLAchol). HLApap and HLAchol are fairly stable proteins to agents acting predominantly on hydrogen bonds (temperature, urea) or hydrophobic forces (ionic and nonionic detergents). However, agents which affect ionic interactions (pH, salts, divalent cations) dissociate the molecules into subunits. A single binding site for beta 2-microglobulin with an affinity constant of 1.0 X 10(7) M-1 was found for the alpha chain of HLAchol. The dissociated subunits can be separated by affinity chromatography on Sepharose-rabbit IgG anti-human beta 2-microglobulin and reassociate in vitro when incubated under the appropriate conditions. The results point toward an important role of ionic interactions between subunits in the stabilization of the quaternary structure of HLA. 相似文献