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61.
siRNA (small interfering RNA) and shRNA (small hairpin RNA) are powerful and commonly used tools in biomedical research. Currently, siRNAs are generally designed as two 21 nt strands of RNA that include a 19 nt completely complementary part and a 2 nt overhang. However, since the si/shRNAs use the endogenous miRNA machinery for gene silencing and the miRNAs are generally 22 nt in length and contain multiple internal mismatches, we tested if the functionality can be increased by designing the si/shRNAs to mimic a miRNA structure. We systematically investigated the effect of single or multiple mismatches introduced in the passenger strand at different positions on siRNA functionality. Mismatches at certain positions could significantly increase the functionality of siRNAs and also, in some cases decreased the unwanted passenger strand functionality. The same strategy could also be used to design shRNAs. Finally, we showed that both si and miRNA structured oligos (siRNA with or without mismatches in the passenger strand) can repress targets in all individual Ago containing cells, suggesting that the Ago proteins do not differentiate between si/miRNA-based structure for silencing activity. 相似文献
62.
Reactions of ligands 1-ethyl-5-methyl-3-phenyl-1H-pyrazole (L1) and 5-methyl-1-octyl-3-phenyl-1H-pyrazole (L2) with [PdCl2(CH3CN)2 and K2PtCl4 gave complexes trans-[MCl2(L)2] (L = L1, L2). The new complexes were characterised by elemental analyses, conductivity measurements, infrared, 1H and 13C{1H} NMR spectroscopies and X-ray diffraction. The NMR study of the complex [PdCl2(L1)2], in CDCl3 solution, is consistent with a very slow rotation of ligands around the Pd-N bond, so that two conformational isomers can be observed in solution (syn and anti). Different behaviour is observed for complexes [PdCl2(L2)2] and [PtCl2(L)2] (L = L1, L2), which present an isomer in solution at room temperature (anti). The crystal structure of [PdCl2(L1)2] complex is described, where the Pd(II) presents a square planar geometry with the ligands coordinated in a trans disposition. 相似文献
63.
Two new pyrazole-derived ligands, 1-ethyl-3,5-bis(2-pyridyl)pyrazole (L1) and 1-octyl-3,5-bis(2-pyridyl)pyrazole (L2), both containing alkyl groups at position 1 were prepared by reaction between 3,5-bis(2-pyridyl) pyrazole and the appropriate bromoalkane in toluene using sodium ethoxide as base.The reaction between L1, L2 and [MCl2(CH3CN)2] (M = Pd(II), Pt(II)) resulted in the formation complexes of formula [MCl2(L)] (M = Pd(II), L = L1 (1); M = Pd(II), L = L2 (2); M = Pt(II), L = L1 (3); M = Pt(II), L = L2 (4)). These complexes were characterised by elemental analyses, conductivity measurements, infrared, 1H, 13C{1H} NMR and HMQC spectroscopies. The X-ray structure of the complex [PtCl2(L2)] (4) was determined. In this complex, Npyridine and Npyrazole donor atoms coordinate the ligand to the metal, which complete its coordination with two chloro ligands in a cis disposition. 相似文献
64.
65.
Jos�� M. Montoya Dave Raffaelli 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2010,365(1549):2013-2018
Climate change is real. The wrangling debates are over, and we now need to move onto a predictive ecology that will allow managers of landscapes and policy makers to adapt to the likely changes in biodiversity over the coming decades. There is ample evidence that ecological responses are already occurring at the individual species (population) level. The challenge is how to synthesize the growing list of such observations with a coherent body of theory that will enable us to predict where and when changes will occur, what the consequences might be for the conservation and sustainable use of biodiversity and what we might do practically in order to maintain those systems in as good condition as possible. It is thus necessary to investigate the effects of climate change at the ecosystem level and to consider novel emergent ecosystems composed of new species assemblages arising from differential rates of range shifts of species. Here, we present current knowledge on the effects of climate change on biotic interactions and ecosystem services supply, and summarize the papers included in this volume. We discuss how resilient ecosystems are in the face of the multiple components that characterize climate change, and suggest which current ecological theories may be used as a starting point to predict ecosystem-level effects of climate change. 相似文献
66.
Classifying glycerol dehydratase by its functional residues and purifying selection in its evolution
Glycerol dehydratase (GD) catalyses glycerol reductive conversion to 3-hydroxypropanaldehyde (3-HPA), this being the first step required for the microbial conversion of glycerol to 1, 3 -propanodiol. GD has been functionally characterised to date and two main groups have been determined, one of them being vitamin B(12)-dependent and the other B(12)-independent. GD evolutionary history has been described and an exhaustive analysis made for detecting the functional residues responsible for type I divergence. GD phylogenetic tree topology was seen to be statistically robust and the data indicated strong purifying selection operating on the GD proteins within it. Two clades were indentified, one for vitamin B(12)-dependent and the other for B(12)- independent classes. The ancient hot-pot residues responsible for protein divergency for each clade were also identified. The basic evolutionary biology for GD proteins has been described, thereby opening the way forward for developing rational mutagenesis studies. 相似文献
67.
Ricardo Sánchez David Pantoja-Uceda Jesús Prieto Tammo Diercks María J. Marcaida Guillermo Montoya Ramón Campos-Olivas Francisco J. Blanco 《The Journal of biological chemistry》2010,285(29):22196-22201
Gadd45α is a nuclear protein encoded by a DNA damage-inducible gene. Through its interactions with other proteins, Gadd45α participates in the regulation of DNA repair, cell cycle, cell proliferation, and apoptosis. The NMR structure of human Gadd45α has been determined and shows an α/β fold with two long disordered and flexible regions at the N terminus and one of the loops. Human Gadd45α is predominantly monomeric in solution but exists in equilibrium with dimers and other oligomers whose population increases with protein concentration. NMR analysis shows that Aurora A interacts through its N-terminal domain with a region of human Gadd45α encompassing the site of dimerization, suggesting that the oligomerization of Gadd45α could be a regulatory mechanism to modulate its interactions with Aurora A, and possibly with other proteins too. However, Gadd45α appears to interact only weakly with PCNA through its flexible loop, in contrast with previous and contradictory reports. 相似文献
68.
69.
Ordway D Harton M Henao-Tamayo M Montoya R Orme IM Gonzalez-Juarrero M 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(8):4931-4939
In this study, we evaluated the cellular influx and cytokine environment in the lungs of mice made immune by prior vaccination with Mycobacterium bovis bacillus Calmette-Guérin compared with control mice after infection with Mycobacterium tuberculosis to characterize composition of protective lesions in the lungs. Immune mice controlled the growth of the M. tuberculosis challenge more efficiently than control mice. In immune animals, granulomatous lesions were smaller and had a more lymphocytic core, less foamy cells, less parenchymal inflammation, and slower progression of lung pathology than in lungs of control mice. During the chronic stage of the infection, the bacterial load in the lungs of immune mice remained at a level 10 times lower than control mice, and this was associated with reduced numbers of CD4P(+P) and CD8P(+P) T cells, and the lower expression of protective (IL-12, IFN-gamma), inflammatory (TNF-alpha), immunoregulatory (GM-CSF), and immunosuppressive (IL-10) cytokines. The immune mice had higher numbers of CD11b- CD11c(high) DEC-205(low) alveolar macrophages, but lower numbers of CD11b+ CD11c(high) DEC-205(high) dendritic cells, with the latter expressing significantly lower levels of the antiapoptotic marker TNFR-associated factor-1. Moreover, during the early stage of chronic infection, lung dendritic cells from immune mice expressed higher levels of MHC class II and CD40 molecules than similar cells from control mice. These results indicate that while a chronic disease state is the eventual outcome in both control and immune mice infected with M. tuberculosis by aerosol exposure, immune mice develop a protective granulomatous lesion by increasing macrophage numbers and reduced expression of protective and inflammatory cytokines. 相似文献
70.
Herrera F Urdaneta L Rivero J Zoghbi N Ruiz J Carrasquel G Martínez JA Pernalete M Villegas P Montoya A Rubio-Palis Y Rojas E 《Memórias do Instituto Oswaldo Cruz》2006,101(6):625-633
The mosquito Aedes aegypti is the main vector of dengue in Venezuela. The genetic structure of this vector was investigated in 24 samples collected from eight geographic regions separated by up to 1160 km. We examined the distribution of a 359-basepair region of the NADH dehydrogenase subunit 4 mitochondrial gene among 1144 Ae. aegypti from eight collections. This gene was amplified by the polymerase chain reaction and tested for variation using single strand conformation polymorphism analysis. Seven haplotypes were detected throughout Venezuela and these were sorted into two clades. Significant differentiation was detected among collections and these were genetically isolated by distance. 相似文献