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51.
52.
McCallum SE Parameswaran N Perez XA Bao S McIntosh JM Grady SR Quik M 《Journal of neurochemistry》2006,96(4):960-972
Clinical symptoms of Parkinson's disease only become evident after 70-80% reductions in striatal dopamine. To investigate the importance of pre-synaptic dopaminergic mechanisms in this compensation, we determined the effect of nigrostriatal damage on dopaminergic markers and function in primates. MPTP treatment resulted in a graded dopamine loss with moderate to severe declines in ventromedial striatum (approximately 60-95%) and the greatest reductions (approximately 95-99%) in dorsolateral striatum. A somewhat less severe pattern of loss was observed for striatal nicotinic receptor, tyrosine hydroxylase and vesicular monoamine transporter expression. Declines in striatal dopamine uptake and transporter sites were also less severe than the reduction in dopamine levels, with enhanced dopamine turnover in the dorsolateral striatum after lesioning. The greatest degree of adaptation occurred for nicotine-evoked [(3)H]dopamine release from striatal synaptosomes, which was relatively intact in ventromedial striatum after lesioning, despite > 50% declines in dopamine. This maintenance of evoked release was not due to compensatory alterations in nicotinic receptor characteristics. Rather, there appeared to be a generalized preservation of release processes in ventromedial striatum, with K(+)-evoked release also near control levels after lesioning. These combined compensatory mechanisms help explain the finding that Parkinson's disease symptomatology develops only with major losses of striatal dopamine. 相似文献
53.
主要探讨了T细胞免疫原TI对口蹄疫疫苗的免疫增强作用。设计并原核表达产生了一种包含口蹄疫病毒VP1,VP4,3A和3D蛋白上多个T细胞表位与两个通用T细胞表位的T细胞免疫原,命名为TI;同时表达了O和Asia 1两个型口蹄疫病毒 VP1 蛋白的串联编码基因,表达产物命名为OA-VP1。将上述T细胞免疫原分别与OA-VP1和口蹄疫灭活疫苗按不同剂量组合免疫小鼠,于免疫后不同时间测定各组小鼠的体液与细胞免疫应答情况。采用微量中和试验检测小鼠O型和Asia1型中和抗体,采用流式细胞检测技术和测定γ-干扰素的水平来分析不同免疫组小鼠细胞免疫的水平。结果显示,与灭活疫苗或OA-VP1单独免疫组相比,添加TI抗原后灭活疫苗 (P<0.01) 和OA-VP1免疫组(P<0.05)小鼠均能产生高水平的特异性中和抗体;且CD4+ T细胞数量显著增多,IFN-γ产生水平显著升高 (P<0.01)。说明TI抗原具有很好的诱导特异性体液与细胞免疫应答的作用,是一种很好的免疫增效剂,可作为口蹄疫蛋白亚单位疫苗和灭活疫苗中的一种有效成分,以提高疫苗的免疫效果。 相似文献
54.
Xiaomin Tang Weidong Bao Wenli Zhang Zhukuan Cheng 《植物学报(英文版)》2007,49(6):953-960
To develop reliable techniques for chromosome identification is critical for cytogenetic research, especially for genomes with a large number and smaller-sized chromosomes. An efficient approach using bacterial artificial chromosome (BAC) clones as molecular cytological markers has been developed for many organisms. Herein, we present a set of chromosomal arm-specific molecular cytological markers derived from the gene-enriched regions of the sequenced rice genome. All these markers are able to generate very strong signals on the pachytene chromosomes of Oryza sativa L. (AA genome) when used as fluorescence in situ hybridization (FISH) probes. We further probed those markers to the pachytene chromosomes of O. punctata (BB genome) and O. officinalis (CC genome) and also got very strong signals on the relevant pachytene chromosomes. The signal position of each marker on the related chromosomes from the three different rice genomes was pretty much stable, which enabled us to identify different chromosomes among various rice genomes. We also constructed the karyotype for both O. punctata and O. officinalis with the BB and CC genomes, respectively, by analysis of 10 pachytene cells anchored by these chromosomal arm-specific markers. 相似文献
55.
Tsai JJ Liu SH Yin SC Yang CN Hsu HS Chen WB Liao EC Lee WJ Pan HC Sheu ML 《PloS one》2011,6(9):e23249
Background
Allergic disease can be characterized as manifestations of an exaggerated inflammatory response to environmental allergens triggers. Mite allergen Der-p2 is one of the major allergens of the house dust mite, which contributes to TLR4 expression and function in B cells in allergic patients. However, the precise mechanisms of Der-p2 on B cells remain obscure.Methodology/Principal Findings
We investigated the effects of Der-p2 on proinflammatory cytokines responses and Toll-like receptor-4 (TLR4)-related signaling in human B cells activation. We demonstrated that Der-p2 activates pro-inflammatory cytokines, TLR4 and its co-receptor MD2. ERK inhibitor PD98059 significantly enhanced TLR4/MD2 expression in Der-p2-treated B cells. Der-p2 markedly activated mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) and decreased p38 phosphorylation in B cells. MKP-1-siRNA downregulated TLR4/MD2 expression in Der-p2-treated B cells. In addition, Der-p2 significantly up-regulated expression of co-stimulatory molecules and increased B cell proliferation. Neutralizing Der-p2 antibody could effectively abrogate the Der-p2-induced B cell proliferation. Der-p2 could also markedly induce NF-κB activation in B cells, which could be counteracted by dexamethasone.Conclusions/Significance
These results strongly suggest that Der-p2 is capable of triggering B cell activation and MKP-1-activated p38/MAPK dephosphorylation-regulated TLR4 induction, which subsequently enhances host immune, defense responses and development of effective allergic disease therapeutics in B cells. 相似文献56.
Chemically sulfated polysaccharide (S-GAP-P) was derived from water-insoluble polysaccharide of Grifola frondosa mycelia. In this research, we investigated the anticancer effects of S-GAP-P and its combination with 5-fluorouracil (5-FU) on human gastric carcinoma SGC-7901 cells. Results showed that S-GAP-P distinctly inhibited SGC-7901 cells growth in a dose-dependent manner and induced cell apoptosis evidenced by characteristic DNA ladder and sub-G0/G1 peak. Furthermore, the combination of S-GAP-P (10–50 μg/ml) with 1 μg/ml 5-FU resulted in a significant inhibition on SGC-7901 cells growth, meaning the beneficial interaction between the two drugs. All these results suggested that S-GAP-P has evident anticancer activity through apoptotic induction and could significantly accelerate the anticancer activity of 5-FU. 相似文献
57.
58.
Climate change poses critical challenges for population persistence in natural communities, for agriculture and environmental sustainability, and for food security. In this review, we discuss recent progress in climatic adaptation in plants. We evaluate whether climate change exerts novel selection and disrupts local adaptation, whether gene flow can facilitate adaptive responses to climate change, and whether adaptive phenotypic plasticity could sustain populations in the short term. Furthermore, we discuss how climate change influences species interactions. Through a more in‐depth understanding of these eco‐evolutionary dynamics, we will increase our capacity to predict the adaptive potential of plants under climate change. In addition, we review studies that dissect the genetic basis of plant adaptation to climate change. Finally, we highlight key research gaps, ranging from validating gene function to elucidating molecular mechanisms, expanding research systems from model species to other natural species, testing the fitness consequences of alleles in natural environments, and designing multifactorial studies that more closely reflect the complex and interactive effects of multiple climate change factors. By leveraging interdisciplinary tools (e.g., cutting‐edge omics toolkits, novel ecological strategies, newly developed genome editing technology), researchers can more accurately predict the probability that species can persist through this rapid and intense period of environmental change, as well as cultivate crops to withstand climate change, and conserve biodiversity in natural systems. 相似文献
59.
Deformable energy storage devices are needed to power next‐generation wearable electronics that interface intimately with human skin. Currently, deformable energy storage devices demonstrate poor performance compared to their rigid lithium‐ion counterparts, forcing wearable manufacturers to design their devices around bulky battery compartments. However, technological advances to create deformable batteries at the component and device level have yielded continuous improvement in stretchable batteries over the last five years. In this Essay, the major strategies at the component and device level that have been successfully employed to create stretchable batteries are reviewed. The outstanding challenges facing deformable energy storage are also discussed, namely, energy density, packaging, delamination, device integration, and manufacturing. This Essay will give researchers who are interested in contributing to the development of deformable batteries a cursory understanding of the most successful strategies to date, and provide insights into the most important directions to pursue in the future. 相似文献
60.
John C. Whitney Christina M. Beck Young Ah Goo Alistair B. Russell Brittany N. Harding Justin A. De Leon David A. Cunningham Bao Q. Tran David A. Low David R. Goodlett Christopher S. Hayes Joseph D. Mougous 《Molecular microbiology》2014,92(3):529-542
Bacterial secretion systems often employ molecular chaperones to recognize and facilitate export of their substrates. Recent work demonstrated that a secreted component of the type VI secretion system (T6SS), haemolysin co‐regulated protein (Hcp), binds directly to effectors, enhancing their stability in the bacterial cytoplasm. Herein, we describe a quantitative cellular proteomics screen for T6S substrates that exploits this chaperone‐like quality of Hcp. Application of this approach to the Hcp secretion island I‐encoded T6SS (H1‐T6SS) of Pseudomonas aeruginosa led to the identification of a novel effector protein, termed Tse4 (t ype VI s ecretion e xported 4), subsequently shown to act as a potent intra‐specific H1‐T6SS‐delivered antibacterial toxin. Interestingly, our screen failed to identify two predicted H1‐T6SS effectors, Tse5 and Tse6, which differ from Hcp‐stabilized substrates by the presence of toxin‐associated PAAR‐repeat motifs and genetic linkage to members of the valine‐glycine repeat protein G (vgrG) genes. Genetic studies further distinguished these two groups of effectors: Hcp‐stabilized effectors were found to display redundancy in interbacterial competition with respect to the requirement for the two H1‐T6SS‐exported VgrG proteins, whereas Tse5 and Tse6 delivery strictly required a cognate VgrG. Together, we propose that interaction with either VgrG or Hcp defines distinct pathways for T6S effector export. 相似文献