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51.
We studied developmental and environmental constraints on leaf dynamics, morphology and physiology in the monopodial tropical palm of the Atlantic Forest biome, Euterpe edulis. Plastic responses to light environments in terms of photosynthesis, leaf size, leaf life span, patterns of biomass allocation and growth were analysed. Plants were grown during 14 months in a shade house under four different growth irradiances. Plants of Euterpe edulis were able to adjust leaf demography and biomass allocation in the different light treatments. Leaf life span increased by 100 days with decreasing light levels while the rate of leaf production decreased, consistent with lower electron transport rates. At low light levels, adjustments in biomass allocation to leaf components allowed E. edulis to reduce self-shading and increase light interception. At high light plants allocated more biomass to roots, and the plants exhibited small leaf sizes when leaves were compared using an explicit ontogenetic analysis. Ontogeny constrained the maximum size that each consecutive leaf could achieve, while growth irradiance determined the rate of leaf production and other leaf traits. Consequently, there were both, developmental constraints and environmental determinants influencing leaf demography and morphology in E. edulis. The findings of this ecophysiological and demographic study are relevant to palms growing under natural conditions and help to explain the success of E. edulis in the forest understory and its absence from large gap openings. Our results not only confirm that E. edulis is a shade tolerant species, but also show that palms are able to acclimate to different growing condition as well as trees. 相似文献
52.
ATM requirement in gene expression responses to ionizing radiation in human lymphoblasts and fibroblasts 总被引:3,自引:0,他引:3
Innes CL Heinloth AN Flores KG Sieber SO Deming PB Bushel PR Kaufmann WK Paules RS 《Molecular cancer research : MCR》2006,4(3):197-207
The heritable disorder ataxia telangiectasia (AT) is caused by mutations in the AT-mutated (ATM) gene with manifestations that include predisposition to lymphoproliferative cancers and hypersensitivity to ionizing radiation (IR). We investigated gene expression changes in response to IR in human lymphoblasts and fibroblasts from seven normal and seven AT-affected individuals. Both cell types displayed ATM-dependent gene expression changes after IR, with some responses shared and some responses varying with cell type and dose. Interestingly, after 5 Gy IR, lymphoblasts displayed ATM-independent responses not seen in the fibroblasts at this dose, which likely reflect signaling through ATM-related kinases, e.g., ATR, in the absence of ATM function. 相似文献
53.
54.
Pei Y Hancock PJ Zhang H Bartz R Cherrin C Innocent N Pomerantz CJ Seitzer J Koser ML Abrams MT Xu Y Kuklin NA Burke PA Sachs AB Sepp-Lorenzino L Barnett SF 《RNA (New York, N.Y.)》2010,16(12):2553-2563
Effective small interfering RNA (siRNA)-mediated therapeutics require the siRNA to be delivered into the cellular RNA-induced silencing complex (RISC). Quantitative information of this essential delivery step is currently inferred from the efficacy of gene silencing and siRNA uptake in the tissue. Here we report an approach to directly quantify siRNA in the RISC in rodents and monkey. This is achieved by specific immunoprecipitation of the RISC from tissue lysates and quantification of small RNAs in the immunoprecipitates by stem-loop PCR. The method, expected to be independent of delivery vehicle and target, is label-free, and the throughput is acceptable for preclinical animal studies. We characterized a lipid-formulated siRNA by integrating these approaches and obtained a quantitative perspective on siRNA tissue accumulation, RISC loading, and gene silencing. The described methodologies have utility for the study of silencing mechanism, the development of siRNA therapeutics, and clinical trial design. 相似文献
55.
Prions are the infectious agents responsible for prion diseases, which appear to be composed exclusively by the misfolded prion protein (PrP(Sc)). Disease is transmitted by the autocatalytic propagation of PrP(Sc) misfolding at the expense of the normal prion protein. The biggest challenge of the prion hypothesis has been to explain the molecular mechanism by which prions can exist as different strains, producing diseases with distinguishable characteristics. Here, we show that PrP(Sc) generated in vitro by protein misfolding cyclic amplification from five different mouse prion strains maintains the strain-specific properties. Inoculation of wild-type mice with in vitro-generated PrP(Sc) caused a disease with indistinguishable incubation times as well as neuropathological and biochemical characteristics as the parental strains. Biochemical features were also maintained upon replication of four human prion strains. These results provide additional support for the prion hypothesis and indicate that strain characteristics can be faithfully propagated in the absence of living cells, suggesting that strain variation is dependent on PrP(Sc) properties. 相似文献
56.
Bonner DK Leung C Chen-Liang J Chingozha L Langer R Hammond PT 《Bioconjugate chemistry》2011,22(8):1519-1525
The delivery of nucleic acids has the potential to revolutionize medicine by allowing previously untreatable diseases to be clinically addressed. Viral delivery systems have shown immunogenicity and toxicity dangers, but synthetic vectors have lagged in transfection efficiency. Previously, we developed a modular, linear-dendritic block copolymer architecture with high gene transfection efficiency compared to commercial standards. This rationally designed system makes use of a cationic dendritic block to condense the anionic DNA and forms complexes with favorable endosomal escape properties. The linear block provides biocompatibility and protection from serum proteins, and can be functionalized with a targeting ligand. In this work, we quantitate performance of this system with respect to intracellular barriers to gene delivery using both high-throughput and traditional approaches. An image-based, high-throughput assay for endosomal escape is described and applied to the block copolymer system. Nuclear entry is demonstrated to be the most significant barrier to more efficient delivery and will be addressed in future versions of the system. 相似文献
57.
58.
Lymphotoxin-alpha-deficient mice make delayed,but effective,T and B cell responses to influenza 总被引:6,自引:0,他引:6
Lund FE Partida-Sánchez S Lee BO Kusser KL Hartson L Hogan RJ Woodland DL Randall TD 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(9):5236-5243
Lymphotoxin-alpha(-/-) (LTalpha(-/-)) mice are thought to be unable to generate effective T and B cell responses. This is attributed to the lack of lymph nodes and the disrupted splenic architecture of these mice. However, despite these defects we found that LTalpha(-/-) mice could survive infection with a virulent influenza A virus. LTalpha(-/-) mice and normal wild-type mice infected with influenza A generated similar numbers of influenza-specific CD8 T cells that were able to produce IFN-gamma and kill target cells presenting influenza peptides. Furthermore influenza-infected LTalpha(-/-) mice produced high titers of influenza-specific IgM, IgG, and IgA. However, both CD8 and B cell immune responses were delayed in LTalpha(-/-) mice by 2-3 days. The delayed cellular and humoral immune response was sufficient to mediate viral clearance in LTalpha(-/-) mice that were infected with relatively low doses of influenza virus. However, when LTalpha(-/-) mice were infected with larger doses of influenza, they succumbed to infection before the immune response was initiated. These results demonstrate that neither LTalpha nor constitutively organized lymphoid tissues, such as lymph nodes and spleen, are absolutely required for the generation of effective immunity against the respiratory virus influenza A. However, the presence of LTalpha and/or lymph nodes does accelerate the initiation of immune responses, which leads to protection from larger doses of virus. 相似文献
59.
60.
Parkinson disease (PD) is a multifactorial neurodegenerative disorder with high incidence in the elderly, where environmental and genetic factors are involved in etiology. In addition, epigenetic mechanisms, including deregulation of DNA methylation have been recently associated to PD. As accurate diagnosis cannot be achieved pre-mortem, identification of early pathological changes is crucial to enable therapeutic interventions before major neuropathological damage occurs. Here we investigated genome-wide DNA methylation in brain and blood samples from PD patients and observed a distinctive pattern of methylation involving many genes previously associated to PD, therefore supporting the role of epigenetic alterations as a molecular mechanism in neurodegeneration. Importantly, we identified concordant methylation alterations in brain and blood, suggesting that blood might hold promise as a surrogate for brain tissue to detect DNA methylation in PD and as a source for biomarker discovery. 相似文献