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91.
Xiao‐Bing Gao Katherine V. Yao Hongling Du John D. Elsworth Hugh S. Taylor 《Journal of cellular and molecular medicine》2011,15(4):747-755
Parkinson’s disease (PD) is a neurodegenerative disorder caused by the loss of dopaminergic neurons. Adult human endometrial derived stem cells (HEDSC), a readily obtainable type of mesenchymal stem‐like cell, were used to generate dopaminergic cells and for transplantation. Cells expressing CD90, platelet derived growth factor (PDGF)‐Rβ and CD146 but not CD45 or CD31 were differentiated in vitro into dopaminergic neurons that exhibited axon projections, pyramidal cell bodies and dendritic projections that recapitulate synapse formation; these cells also expressed the neural marker nestin and tyrosine hydroxylase, the rate‐limiting enzyme in dopamine synthesis. Whole cell patch clamp recording identified G‐protein coupled inwardly rectifying potassium current 2 channels characteristic of central neurons. A 1‐methyl 4‐phenyl 1,2,3,6‐tetrahydro pyridine induced animal model of PD was used to demonstrate the ability of labelled HEDSC to engraft, migrate to the site of lesion, differentiate in vivo and significantly increase striatal dopamine and dopamine metabolite concentrations. HEDSC are a highly inducible source of allogenic stem cells that rescue dopamine concentrations in an immunocompetent PD mouse model. 相似文献
92.
Giuseppe Battaglia Milena Cannella Barbara Riozzi Sara Orobello Marion L. Maat‐Schieman Eleonora Aronica Carla Letizia Busceti Andrea Ciarmiello Silvia Alberti Enrico Amico Jenny Sassone Simonetta Sipione Valeria Bruno Luigi Frati Ferdinando Nicoletti Ferdinando Squitieri 《Journal of cellular and molecular medicine》2011,15(3):555-571
A defective expression or activity of neurotrophic factors, such as brain‐ and glial‐derived neurotrophic factors, contributes to neuronal damage in Huntington’s disease (HD). Here, we focused on transforming growth factor‐β (TGF‐β1), a pleiotropic cytokine with an established role in mechanisms of neuroprotection. Asymptomatic HD patients showed a reduction in TGF‐β1 levels in the peripheral blood, which was related to trinucleotide mutation length and glucose hypometabolism in the caudate nucleus. Immunohistochemical analysis in post‐mortem brain tissues showed that TGF‐β1 was reduced in cortical neurons of asymptomatic and symptomatic HD patients. Both YAC128 and R6/2 HD mutant mice showed a reduced expression of TGF‐β1 in the cerebral cortex, localized in neurons, but not in astrocytes. We examined the pharmacological regulation of TGF‐β1 formation in asymptomatic R6/2 mice, where blood TGF‐β1 levels were also reduced. In these R6/2 mice, both the mGlu2/3 metabotropic glutamate receptor agonist, LY379268, and riluzole failed to increase TGF‐β1 formation in the cerebral cortex and corpus striatum, suggesting that a defect in the regulation of TGF‐β1 production is associated with HD. Accordingly, reduced TGF‐β1 mRNA and protein levels were found in cultured astrocytes transfected with mutated exon 1 of the human huntingtin gene, and in striatal knock‐in cell lines expressing full‐length huntingtin with an expanded glutamine repeat. Taken together, our data suggest that serum TGF‐β1 levels are potential biomarkers of HD development during the asymptomatic phase of the disease, and raise the possibility that strategies aimed at rescuing TGF‐β1 levels in the brain may influence the progression of HD. 相似文献
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Aidin Niamir Andrew K. Skidmore Albertus G. Toxopeus Antonio R. Muñoz Raimundo Real 《Diversity & distributions》2011,17(6):1173-1185
Aim The spatial resolution of species atlases and therefore resulting model predictions are often too coarse for local applications. Collecting distribution data at a finer resolution for large numbers of species requires a comprehensive sampling effort, making it impractical and expensive. This study outlines the incorporation of existing knowledge into a conventional approach to predict the distribution of Bonelli’s eagle (Aquila fasciata) at a resolution 100 times finer than available atlas data. Location Malaga province, Andalusia, southern Spain. Methods A Bayesian expert system was proposed to utilize the knowledge from distribution models to yield the probability of a species being recorded at a finer resolution (1 × 1 km) than the original atlas data (10 × 10 km). The recorded probability was then used as a weight vector to generate a sampling scheme from the species atlas to enhance the accuracy of the modelling procedure. The maximum entropy for species distribution modelling (MaxEnt) was used as the species distribution model. A comparison was made between the results of the MaxEnt using the enhanced and, the random sampling scheme, based on four groups of environmental variables: topographic, climatic, biological and anthropogenic. Results The models with the sampling scheme enhanced by an expert system had a higher discriminative capacity than the baseline models. The downscaled (i.e. finer scale) species distribution maps using a hybrid MaxEnt/expert system approach were more specific to the nest locations and were more contrasted than those of the baseline model. Main conclusions The proposed method is a feasible substitute for comprehensive field work. The approach developed in this study is applicable for predicting the distribution of Bonelli’s eagle at a local scale from a national‐level occurrence data set; however, the usefulness of this approach may be limited to well‐known species. 相似文献
95.
The purposeful introduction of the land snail Euglandina rosea, which feeds exclusively on snails and slugs, has been implicated as a major factor in the decline of diverse Pacific island land snail faunas. We report on the distribution, movement patterns, and microhabitat preferences of E. rosea in a gulch in the Waianae Mountains, Oahu, Hawaii, because such data will help focus management actions at a local scale to protect native snail populations in areas where E. rosea is established. The Waianae Mountains harbor many endangered or threatened snails, most currently found in isolated habitat patches near the ridges. Conversely, most living individuals (28/29) and shells (46/56) of E. rosea were collected within the gulch, which supported higher densities of other native and non‐native snails, and was cooler and more moist than the ridges. Thirteen individuals of E. rosea were tracked (eight directly using a bobbin and thread method, and five indirectly by mark–recapture); most (10/13) moved on average <2.5 m per week (range 0.1–25.21 m), and all stayed within the gulch. Members of E. rosea preferred leaf litter over open, fern/shrub, or wood microhabitats. There were large differences in the population density of E. rosea over small spatial scales, indicating that there may be places where native snail populations could persist even in areas where populations of E. rosea are established. Identifying areas with differing population densities of E. rosea is critical for not only understanding why some native snail species may be more vulnerable to extinction, but also to locate areas where predation pressure is low and conservation efforts will be most likely to succeed. 相似文献
96.
Viruses express viral suppressors of RNA silencing (VSRs) to counteract RNA silencing-based host defenses. Although virtually all stages of the antiviral silencing pathway can be inhibited by VSRs, small RNAs (sRNAs) and Argonaute (AGO) proteins seem to be the most frequent targets. Recently, GW/WG motifs of some VSRs have been proposed to dictate their suppressor function by mediating interaction with AGO(s). Here we have studied the VSR encoded by Pelargonium line pattern virus (family Tombusviridae). The results show that p37, the viral coat protein, blocks RNA silencing. Site-directed mutagenesis of some p37 sequence traits, including a conserved GW motif, allowed generation of suppressor-competent and -incompetent molecules and uncoupling of the VSR and particle assembly capacities. The engineered mutants were used to assess the importance of p37 functions for viral infection and the relative contribution of diverse molecular interactions to suppressor activity. Two main conclusions can be drawn: (i) the silencing suppression and encapsidation functions of p37 are both required for systemic Pelargonium line pattern virus infection, and (ii) the suppressor activity of p37 relies on the ability to bind sRNAs rather than on interaction with AGOs. The data also caution against potential misinterpretations of results due to overlap of sequence signals related to distinct protein properties. This is well illustrated by mutation of the GW motif in p37 that concurrently affects nucleolar localization, efficient interaction with AGO1, and sRNA binding capability. These concomitant effects could have been overlooked in other GW motif-containing suppressors, as we exemplify with the orthologous p38 of turnip crinkle virus. 相似文献
97.
Lin Yuan Zhongbin Chen Shanshan Song Shan Wang Chunyan Tian Guichun Xing Xiaojuan Chen Zhi-Xiong Xiao Fuchu He Lingqiang Zhang 《The Journal of biological chemistry》2015,290(5):3172-3182
Infection by human coronaviruses is usually characterized by rampant viral replication and severe immunopathology in host cells. Recently, the coronavirus papain-like proteases (PLPs) have been identified as suppressors of the innate immune response. However, the molecular mechanism of this inhibition remains unclear. Here, we provide evidence that PLP2, a catalytic domain of the nonstructural protein 3 of human coronavirus NL63 (HCoV-NL63), deubiquitinates and stabilizes the cellular oncoprotein MDM2 and induces the proteasomal degradation of p53. Meanwhile, we identify IRF7 (interferon regulatory factor 7) as a bona fide target gene of p53 to mediate the p53-directed production of type I interferon and the innate immune response. By promoting p53 degradation, PLP2 inhibits the p53-mediated antiviral response and apoptosis to ensure viral growth in infected cells. Thus, our study reveals that coronavirus engages PLPs to escape from the innate antiviral response of the host by inhibiting p53-IRF7-IFNβ signaling. 相似文献
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综述了利用植物病毒载体过量表达或抑制基因表达方面的研究进展.这些技术的发展为工业制药和功能基因组学的研究提供了有力的研究工具.对病毒载体在应用中的局限性及其前景进行了分析. 相似文献