全文获取类型
收费全文 | 1103篇 |
免费 | 78篇 |
出版年
2023年 | 19篇 |
2022年 | 21篇 |
2021年 | 33篇 |
2020年 | 35篇 |
2019年 | 36篇 |
2018年 | 40篇 |
2017年 | 47篇 |
2016年 | 56篇 |
2015年 | 55篇 |
2014年 | 64篇 |
2013年 | 89篇 |
2012年 | 92篇 |
2011年 | 83篇 |
2010年 | 51篇 |
2009年 | 34篇 |
2008年 | 61篇 |
2007年 | 36篇 |
2006年 | 53篇 |
2005年 | 33篇 |
2004年 | 33篇 |
2003年 | 32篇 |
2002年 | 27篇 |
2001年 | 23篇 |
2000年 | 25篇 |
1999年 | 17篇 |
1998年 | 3篇 |
1997年 | 8篇 |
1996年 | 6篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 5篇 |
1990年 | 7篇 |
1989年 | 6篇 |
1988年 | 6篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1967年 | 1篇 |
1966年 | 1篇 |
1960年 | 1篇 |
排序方式: 共有1181条查询结果,搜索用时 171 毫秒
41.
Carla D. Jorge Nuno Borges Irina Bagyan Andreas Bilstein Helena Santos 《Extremophiles : life under extreme conditions》2016,20(3):251-259
Protein misfolding, aggregation and deposition in the brain, in the form of amyloid, are implicated in the etiology of several neurodegenerative disorders, such as Alzheimer’s, Parkinson’s and prion diseases. Drugs available on the market reduce the symptoms, but they are not a cure. Therefore, it is urgent to identify promising targets and develop effective drugs. Preservation of protein native conformation and/or inhibition of protein aggregation seem pertinent targets for drug development. Several studies have shown that organic solutes, produced by extremophilic microorganisms in response to osmotic and/or heat stress, prevent denaturation and aggregation of model proteins. Among these stress solutes, mannosylglycerate, mannosylglyceramide, di-myo-inositol phosphate, diglycerol phosphate and ectoine are effective in preventing amyloid formation by Alzheimer’s Aβ peptide and/or α-synuclein in vitro. Moreover, mannosylglycerate is a potent inhibitor of Aβ and α-synuclein aggregation in living cells, and mannosylglyceramide and ectoine inhibit aggregation and reduce prion peptide-induced toxicity in human cells. This review focuses on the efficacy of stress solutes from hyper/thermophiles and ectoines to prevent amyloid formation in vitro and in vivo and their potential application in drug development against protein misfolding diseases. Current and envisaged applications of these extremolytes in neurodegenerative diseases and healthcare will also be addressed. 相似文献
42.
Manuel J. Steinbauer Richard Field John‐Arvid Grytnes Panayiotis Trigas Claudine Ah‐Peng Fabio Attorre H. John B. Birks Paulo A. V. Borges Pedro Cardoso Chang‐Hung Chou Michele De Sanctis Miguel M. de Sequeira Maria C. Duarte Rui B. Elias José María Fernández‐Palacios Rosalina Gabriel Roy E. Gereau Rosemary G. Gillespie Josef Greimler David E. V. Harter Tsurng‐Juhn Huang Severin D. H. Irl Daniel Jeanmonod Anke Jentsch Alistair S. Jump Christoph Kueffer Sandra Nogué Rüdiger Otto Jonathan Price Maria M. Romeiras Dominique Strasberg Tod Stuessy Jens‐Christian Svenning Ole R. Vetaas Carl Beierkuhnlein 《Global Ecology and Biogeography》2016,25(9):1097-1107
43.
Patrícia T. Borges Célia V. Romão Lígia M. Saraiva Vera L. Gonçalves Maria A. Carrondo Miguel Teixeira Carlos Frazão 《Journal of structural biology》2019,205(1):91-102
Flavodiiron proteins (FDPs) play key roles in biological response mechanisms against oxygen and/or nitric oxide; in particular they are present in oxygenic phototrophs (including cyanobacteria and gymnosperms). Two conserved domains define the core of this family of proteins: a N-terminal metallo-β-lactamase-like domain followed by a C-terminal flavodoxin-like one, containing the catalytic diiron centre and a FMN cofactor, respectively. Members of the FDP family may present extra modules in the C-terminus, and were classified into several classes according to their distribution and composition. The cyanobacterium Synechocystis sp. PCC6803 contains four Class C FDPs (Flv1-4) that include at the C-terminus an additional NAD(P)H:flavin oxidoreductase (FlR) domain. Two of them (Flv3 and Flv4) have the canonical diiron ligands (Class C, Type 1), while the other two (Flv1 and Flv2) present different residues in that region (Class C, Type 2). Most phototrophs, either Bacterial or Eukaryal, contain at least two FDP genes, each encoding for one of those two types. Crystals of the Flv1 two core domains (Flv1-ΔFlR), without the C-terminal NAD(P)H:flavin oxidoreductase extension, were obtained and the structure was determined. Its pseudo diiron site contains non-canonical basic and neutral residues, and showed anion moieties, instead. The presented structure revealed for the first time the structure of the two-domain core of a Class C-Type 2 FDP. 相似文献
44.
Leipold E DeBie H Zorn S Borges A Olivera BM Terlau H Heinemann SH 《Channels (Austin, Tex.)》2007,1(4):253-262
The muO-conotoxins MrVIA and MrVIB are 31-residue peptides from Conus marmoreus, belonging to the O-superfamily of conotoxins with three disulfide bridges. They have attracted attention because they are inhibitors of tetrodotoxin-insensitive voltage-gated sodium channels (Na(V)1.8) and could therefore serve as lead structure for novel analgesics. The aim of this study was to elucidate the molecular mechanism by which muO-conotoxins affect Na(V) channels. Rat Na(V)1.4 channels and mutants thereof were expressed in mammalian cells and were assayed with the whole-cell patch-clamp method. Unlike for the M-superfamily mu-conotoxin GIIIA from Conus geographus, channel block by MrVIA was strongly diminished after activating the Na(V) channels by depolarizing voltage steps. Searching for the source of this voltage dependence, the gating charges in all four-voltage sensors were reduced by site-directed mutagenesis showing that alterations of the voltage sensor in domain-2 have the strongest impact on MrVIA action. These results, together with previous findings that the effect of MrVIA depends on the structure of the pore-loop in domain-3, suggest a functional similarity with scorpion beta-toxins. In fact, MrVIA functionally competed with the scorpion beta-toxin Ts1 from Tityus serrulatus, while it did not show competition with mu-GIIIA. Ts1 and mu-GIIIA did not compete either. Thus, similar to scorpion beta-toxins, muO-conotoxins are voltage-sensor toxins targeting receptor site-4 on Na(V) channels. They "block" Na(+) flow most likely by hindering the voltage sensor in domain-2 from activating and, hence, the channel from opening. 相似文献
45.
Santos LC Ramos EA Gurgel CA de Santana EJ Dos Santos JN 《Journal of molecular histology》2007,38(3):201-205
Objective Dental granulomas (DGs) and radicular cysts (RCs) are chronic periapical lesions frequently involving the jaws. Langerhans
cells (LCs) are dendritic cells responsible for the presentation of antigens to T lymphocytes. This study examined the expression
of LCs in DG and RCs by immunohistochemical staining.
Study Design Eighteen cases of DGs and 26 cases of RCs were analyzed using anti-CD1a marker.
Results CD1a-labeled LCs were observed in 11.1% of DGs and in 69.2% of RCs, showing a significant correlation (P < 0.0001; Fisher’s test). In DGs, LCs were only observed in granulation tissue, showing discrete immunostaining density.
In RCs, LCs exhibited both a round and a dendritic shape in all epithelial layers. Although a correlation was observed between
immunostaining density and epithelial thickness, as well as between immunostaining and inflammatory intensity, the differences
were not significant in radicular cysts.
Conclusion Langerhans cells provide important insight into the immunopathogenesis of chronic periapical lesions. 相似文献
46.
Amaral Joo Henrique Fernandes Melack John Michael Barbosa Pedro Maia Borges Alberto V. Kasper Daniele Corts Alicia Cortes Zhou Wencai MacIntyre Sally Forsberg Bruce Rider 《Ecosystems》2022,25(4):911-930
Ecosystems - Extensive floodplains and numerous lakes in the Amazon basin are well suited to examine the role of floodable lands within the context of the sources and processing of carbon within... 相似文献
47.
Srgio Henrique Borges Fabricio Baccaro Marcelo Moreira Erik Lacerda Choueri 《Biotropica》2019,51(6):903-912
The principles of island biogeography are rarely applied to the animal assemblages of Amazonian river islands. Here, we compare bird assemblages of Amazonian river islands with a variety of mainland habitats. We also examine how bird species diversity and composition are related to island physical attributes. Birds were sampled with mist nets and qualitative censuses on 11 river islands and 24 mainland sites on the lower reaches of the Rio Negro in the Brazilian Amazon. Island bird assemblages were characterized by lower species richness and a higher abundance of a few dominant species. Additionally, the species composition of the islands was distinct from that of the mainland, including the nearby floodplain habitats. The number of bird species increased with island size and habitat diversity, and decreased with degree of isolation. In addition, small islands tended to harbor an impoverished subset of the species present on larger ones. Bird species diversity and composition on Amazonian river islands are likely influenced by the ecological succession and historical events affecting island formation. Considering their small total area across the Amazon basin, these insular fluvial communities could be disproportionately threatened by river channel disturbances related to climate change or hydroelectric dam development. Abstract in Portughese is available with online material. 相似文献
48.
49.
50.
de Oliveira Hellen Oliveira de Castro Gledson Luiz Salgado Correa Lorena Oliveira Silvestre Walter Vellasco Duarte do Nascimento Sidney Vasconcelos da Silva Valadares Rafael Borges de Oliveira Guilherme Corrêa Santos Rodolfo Inacio Nunes Festucci-Buselli Reginaldo Alves Pinheiro Hugo Alves 《Photosynthesis research》2019,140(2):189-205
Photosynthesis Research - This study examined whether drought sensitivity in açaí (Euterpe oleracea Mart.) is associated with reductions in photosynthesis and increasing oxidative stress... 相似文献