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41.
Haefeli RH Erb M Gemperli AC Robay D Courdier Fruh I Anklin C Dallmann R Gueven N 《PloS one》2011,6(3):e17963
Short-chain quinones are described as potent antioxidants and in the case of idebenone have already been under clinical investigation for the treatment of neuromuscular disorders. Due to their analogy to coenzyme Q10 (CoQ10), a long-chain quinone, they are widely regarded as a substitute for CoQ10. However, apart from their antioxidant function, this provides no clear rationale for their use in disorders with normal CoQ10 levels. Using recombinant NAD(P)H:quinone oxidoreductase (NQO) enzymes, we observed that contrary to CoQ10 short-chain quinones such as idebenone are good substrates for both NQO1 and NQO2. Furthermore, the reduction of short-chain quinones by NQOs enabled an antimycin A-sensitive transfer of electrons from cytosolic NAD(P)H to the mitochondrial respiratory chain in both human hepatoma cells (HepG2) and freshly isolated mouse hepatocytes. Consistent with the substrate selectivity of NQOs, both idebenone and CoQ1, but not CoQ10, partially restored cellular ATP levels under conditions of impaired complex I function. The observed cytosolic-mitochondrial shuttling of idebenone and CoQ1 was also associated with reduced lactate production by cybrid cells from mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) patients. Thus, the observed activities separate the effectiveness of short-chain quinones from the related long-chain CoQ10 and provide the rationale for the use of short-chain quinones such as idebenone for the treatment of mitochondrial disorders. 相似文献
42.
The structural and electrochemical consequences of hydrogenating copper N2S2 Schiff base macrocycles
Katherine D. Trotter John C. Forgie Leonard E.A. Berlouis Corinne M. Spickett 《Inorganica chimica acta》2010,363(7):1529-2594
A series of cis and trans tetradentate copper macrocyclic complexes, of ring size 14-16, that employ amine and thioether donor groups are reported. Apart from 5,6,15,16-bisbenzo-8,13-diaza-1,4-dithia-cyclohexadecane copper(I) (cis-[Cu(H4NbuSen)]+) all of the complexes are obtained in the copper(II) form. Crystallographic analysis shows that the copper(II) complexes all adopt a distorted planar geometry around the copper. In contrast, cis-[Cu(H4NbuSen)]+ is found to adopt a distorted tetrahedral geometry. The complexes were subjected to electrochemical analysis in water and acetonitrile. The effect of the solvent, positions of the donor atoms (cis/trans) on E1/2 is discussed as is the comparison of the electrochemical behaviour of these complexes with their parent Schiff base macrocycles. 相似文献
43.
Toxic metal accumulation in soils of agricultural interest is a serious problem needing more attention, and investigations
on soil–plant metal transfer must be pursued to better understand the processes involved in metal uptake. Arbuscular mycorrhizal
(AM) fungi are known to influence metal transfer in plants by increasing plant biomass and reducing metal toxicity to plants
even if diverging results were reported. The effects of five AM fungi isolated from metal contaminated or non-contaminated
soils on metal (Cd, Zn) uptake by plant and transfer to leachates was assessed with Medicago truncatula grown in a multimetallic contaminated agricultural soil. Fungi isolated from metal-contaminated soils were more effective
to reduce shoot Cd concentration. Metal uptake capacity differed between AM fungi and depended on the origin of the isolate.
Not only fungal tolerance and ability to reduce metal concentrations in plant but also interactions with rhizobacteria affected
heavy metal transfer and plant growth. Indeed, thanks to association with nodulating rhizobacteria, one Glomus intraradices inoculum increased particularly plant biomass which allowed exporting twofold more Cd and Zn in shoots as compared to non-mycorrhizal
treatment. Cd concentrations in leachates were variable among fungal treatments, but can be significantly influenced by AM
inoculation. The differential strategies of AM fungal colonisation in metal stress conditions are also discussed. 相似文献
44.
45.
Over time, organisms developed various strategies to adapt to their environment. Circadian clocks are thought to have evolved to adjust to the predictable rhythms of the light-dark cycle caused by the rotation of the Earth around its own axis. The rhythms these clocks generate persist even in the absence of environmental cues with a period of about 24 hours. To tick in time, they continuously synchronize themselves to the prevailing photoperiod by appropriate phase shifts. In this study, we disrupted two molecular components of the mammalian circadian oscillator, Rev-Erbα and Period1 (Per1). We found that mice lacking these genes displayed robust circadian rhythms with significantly shorter periods under constant darkness conditions. Strikingly, they showed high amplitude resetting in response to a brief light pulse at the end of their subjective night phase, which is rare in mammals. Surprisingly, Cry1, a clock component not inducible by light in mammals, became slightly inducible in these mice. Taken together, Rev-Erbα and Per1 may be part of a mechanism preventing drastic phase shifts in mammals. 相似文献
46.
Claudia R. Oliva Susan E. Nozell Anne Diers Samuel G. McClugage III Jann N. Sarkaria James M. Markert Victor M. Darley-Usmar Shannon M. Bailey G. Yancey Gillespie Aimee Landar Corinne E. Griguer 《The Journal of biological chemistry》2010,285(51):39759-39767
Temozolomide (TMZ) is an oral alkylating agent used for the treatment of high-grade gliomas. Acquired chemoresistance is a severe limitation to this therapy with more than 90% of recurrent gliomas showing no response to a second cycle of chemotherapy. Efforts to better understand the underlying mechanisms of acquired chemoresistance to TMZ and potential strategies to overcome chemoresistance are, therefore, critically needed. TMZ methylates nuclear DNA and induces cell death; however, the impact on mitochondria DNA (mtDNA) and mitochondrial bioenergetics is not known. Herein, we tested the hypothesis that TMZ-mediated alterations in mtDNA and respiratory function contribute to TMZ-dependent acquired chemoresistance. Using an in vitro model of TMZ-mediated acquired chemoresistance, we report 1) a decrease in mtDNA copy number and the presence of large heteroplasmic mtDNA deletions in TMZ-resistant glioma cells, 2) remodeling of the entire electron transport chain with significant decreases of complexes I and V and increases of complexes II/III and IV, and 3) pharmacologic and genetic manipulation of cytochrome c oxidase, which restores sensitivity to TMZ-dependent apoptosis in resistant glioma cells. Importantly, human primary and recurrent pairs of glioblastoma multiforme (GBM) biopsies as well as primary and TMZ-resistant GBM xenograft lines exhibit similar remodeling of the ETC. Overall these results suggest that TMZ-dependent acquired chemoresistance may be due to a mitochondrial adaptive response to TMZ genotoxic stress with a major contribution from cytochrome c oxidase. Thus, abrogation of this adaptive response may reverse chemoresistance and restore sensitivity to TMZ, providing a strategy for improved therapeutic outcomes in GBM patients. 相似文献
47.
Julie Dufour Aurélien Pommier Georges Alves Hugues De Boussac Corinne Lours-Calet David H. Volle Jean-Marc A. Lobaccaro Silvère Baron 《PloS one》2013,8(3)
Recent studies underline the implication of Liver X Receptors (LXRs) in several prostate diseases such as benign prostatic hyperplasia (BPH) and prostate cancer. In order to understand the molecular mechanisms involved, we derived epithelial cells from dorsal prostate (MPECs) of wild type (WT) or Lxrαβ−/− mice. In the WT MPECs, our results show that LXR activation reduces proliferation and correlates with the modification of the AKT-survival pathway. Moreover, LXRs regulate lipid homeostasis with the regulation of Abca1, Abcg1 and Idol, and, in a lesser extent, Srebp1, Fas and Acc. Conversely cells derived from Lxrαβ−/− mice show a higher basal phosphorylation and consequently activation of the survival/proliferation transduction pathways AKT and MAPK. Altogether, our data point out that the cell model we developed allows deciphering the molecular mechanisms inducing the cell cycle arrest. Besides, we show that activated LXRs regulate AKT and MAPK transduction pathways and demonstrate that LXRs could be good pharmacological targets in prostate disease such as cancer. 相似文献
48.
Virtual plants: modelling as a tool for the genomics of tolerance to water deficit 总被引:10,自引:0,他引:10
Tardieu F 《Trends in plant science》2003,8(1):9-14
Modelling can simulate the responses of virtual plants carrying diverse combinations of alleles under different scenarios of abiotic stress. The main difficulty is mathematically expressing the genetic variability of responses to environmental conditions. Modelling via gene regulatory networks is not feasible for such complex systems, but plants can be modelled using response curves to environmental conditions that are 'meta mechanisms' at plant level. Each genotype is represented by a set of response parameters that are valid under a wide range of conditions. Transgenesis of one function experimentally affected one response parameter only. Transgenic plants or plants carrying any combination of quantitative trait loci might therefore be simulated and tested under different climatic scenarios, before genetic manipulations are performed. 相似文献
49.
Janko K Marshall C Musilová Z Van Houdt J Couloux A Cruaud C Lecointre G 《Molecular phylogenetics and evolution》2011,60(3):305-316
Clades that have undergone episodes of rapid cladogenesis are challenging from a phylogenetic point of view. They are generally characterised by short or missing internal branches in phylogenetic trees and by conflicting topologies among individual gene trees. This may be the case of the subfamily Trematominae, a group of marine teleosts of coastal Antarctic waters, which is considered to have passed through a period of rapid diversification. Despite much phylogenetic attention, the relationships among Trematominae species remain unclear. In contrast to previous studies that were mostly based on concatenated datasets of mitochondrial and/or single nuclear loci, we applied various single-locus and multilocus phylogenetic approaches to sequences from 11 loci (eight nuclear) and we also used several methods to assess the hypothesis of a radiation event in Trematominae evolution. Diversification rate analyses support the hypothesis of a period of rapid diversification during Trematominae history and only a few nodes in the hypothetical species tree were consistently resolved with various phylogenetic methods. We detected significant discrepancies among trees from individual genes of these species, most probably resulting from incomplete lineage sorting, suggesting that concatenation of loci is not the most appropriate way to investigate Trematominae species interrelationships. These data also provide information about the possible effects of historic climate changes on the diversification rate of this group of fish. 相似文献
50.
Baraguey C Skouri-Panet F Bontems F Tardieu A Chassaing G Lequin O 《Journal of biomolecular NMR》2004,30(3):385-386