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91.
CD8+ T cells are responsible for killing cells of the body that have become infected or oncogenically transformed. In order to do so, effector CD8+ T cells must recognize their cognate antigenic peptide bound to a MHC class I molecule that has been directly presented by the target cell. Due to the rapid nature of antigen presentation, it is believed that antigenic peptides are derived from a subset of newly synthesized proteins which are degraded almost immediately following synthesis and termed Defective Ribosomal Products or DRiPs. We have recently reported on a bioassay which can distinguish antigen presentation of DRiP substrates from other forms of rapidly degraded proteins and found that poly-ubiquitin chain disassembly may be necessary for efficient DRiP presentation. The AAA ATPase p97 protein is necessary for efficient cross-presentation of antigens on MHC class I molecules and plays an important role in extracting mis-folded proteins from the endoplasmic reticulum. Here, we find that genetic ablation or chemical inhibition of p97 does not diminish DRiP antigen presentation to any great extent nor does it alter the levels of MHC class I molecules on the cell surface, despite our observations that p97 inhibition increased the levels of poly-ubiquitinated proteins in the cell. These data demonstrate that inhibiting poly-ubiquitin chain disassembly alone is insufficient to abolish DRiP presentation. 相似文献
92.
Amy C. Burrows John Prokop Matthew K. Summers 《The Journal of biological chemistry》2012,287(46):39021-39029
Ubiquitin-mediated proteolysis is a key regulatory process in cell cycle progression. The Skp1-Cul1-F-box (SCF) and anaphase-promoting complex (APC) ubiquitin ligases target numerous components of the cell cycle machinery for destruction. Throughout the cell cycle, these ligases cooperate to maintain precise levels of key regulatory proteins, and indirectly, each other. Recently, we have identified the deubiquitinase USP37 as a regulator of the cell cycle. USP37 expression is cell cycle-regulated, being expressed in late G1 and ubiquitinated by APCCdh1 in early G1. Here we report that in addition to destruction at G1, a major fraction of USP37 is degraded at the G2/M transition, prior to APC substrates and similar to SCFβTrCP substrates. Consistent with this hypothesis, USP37 interacts with components of the SCF in a βTrCP-dependent manner. Interaction with βTrCP and subsequent degradation is phosphorylation-dependent and is mediated by the Polo-like kinase (Plk1). USP37 is stabilized in G2 by depletion of βTrCP as well as chemical or genetic manipulation of Plk1. Similarly, mutation of the phospho-sites abolishes βTrCP binding and renders USP37 resistant to Plk1 activity. Expression of this mutant hinders the G2/M transition. Our data demonstrate that tight regulation of USP37 levels is required for proper cell cycle progression. 相似文献
93.
94.
Marissa R. Lee Brad Oberle Wendy Olivas Darcy F. Young Amy E. Zanne 《Environmental microbiology》2020,22(11):4702-4717
Diverse communities of fungi and bacteria in deadwood mediate wood decay. While rates of decomposition vary greatly among woody species and spatially distinct habitats, the relative importance of these factors in structuring microbial communities and whether these shift over time remains largely unknown. We characterized fungal and bacterial diversity within pieces of deadwood that experienced 6.3–98.8% mass loss while decaying in common garden ‘rotplots’ in a temperate oak-hickory forest in the Ozark Highlands, MO, USA. Communities were isolated from 21 woody species that had been decomposing for 1–5 years in spatially distinct habitats at the landscape scale (top and bottom of watersheds) and within stems (top and bottom of stems). Microbial community structure varied more strongly with wood traits than with spatial locations, mirroring the relative role of these factors on decay rates on the same pieces of wood even after 5 years. Co-occurring fungal and bacterial communities persistently influenced one another independently from their shared environmental conditions. However, the relative influence of wood construction versus spatial locations differed between fungi and bacteria, suggesting that life history characteristics of these clades structure diversity differently across space and time in decomposing wood. 相似文献
95.
Amy E. Zanne Kessy Abarenkov Michelle E. Afkhami Carlos A. Aguilar‐Trigueros Scott Bates Jennifer M. Bhatnagar Posy E. Busby Natalie Christian William K. Cornwell Thomas W. Crowther Habacuc Flores‐Moreno Dimitrios Floudas Romina Gazis David Hibbett Peter Kennedy Daniel L. Lindner Daniel S. Maynard Amy M. Milo Rolf Henrik Nilsson Jeff Powell Mark Schildhauer Jonathan Schilling Kathleen K. Treseder 《Biological reviews of the Cambridge Philosophical Society》2020,95(2):409-433
Fungi play many essential roles in ecosystems. They facilitate plant access to nutrients and water, serve as decay agents that cycle carbon and nutrients through the soil, water and atmosphere, and are major regulators of macro‐organismal populations. Although technological advances are improving the detection and identification of fungi, there still exist key gaps in our ecological knowledge of this kingdom, especially related to function . Trait‐based approaches have been instrumental in strengthening our understanding of plant functional ecology and, as such, provide excellent models for deepening our understanding of fungal functional ecology in ways that complement insights gained from traditional and ‐omics‐based techniques. In this review, we synthesize current knowledge of fungal functional ecology, taxonomy and systematics and introduce a novel database of fungal functional traits (FunFun). FunFun is built to interface with other databases to explore and predict how fungal functional diversity varies by taxonomy, guild, and other evolutionary or ecological grouping variables. To highlight how a quantitative trait‐based approach can provide new insights, we describe multiple targeted examples and end by suggesting next steps in the rapidly growing field of fungal functional ecology. 相似文献
96.
97.
Emily C. Funk Catriona Breen Bhargav D. Sanketi Natasza Kurpios Amy McCune 《Evolution & development》2020,22(5):384-402
The key to understanding the evolutionary origin and modification of phenotypic traits is revealing the responsible underlying developmental genetic mechanisms. An important organismal trait of ray‐finned fishes is the gas bladder, an air‐filled organ that, in most fishes, functions for buoyancy control, and is homologous to the lungs of lobe‐finned fishes. The critical morphological difference between lungs and gas bladders, which otherwise share many characteristics, is the general direction of budding during development. Lungs bud ventrally and the gas bladder buds dorsally from the anterior foregut. We investigated the genetic underpinnings of this ventral‐to‐dorsal shift in budding direction by studying the expression patterns of known lung genes (Nkx2.1, Sox2, and Bmp4) during the development of lungs or gas bladder in three fishes: bichir, bowfin, and zebrafish. Nkx2.1 and Sox2 show reciprocal dorsoventral expression patterns during tetrapod lung development and are important regulators of lung budding; their expression during bichir lung development is conserved. Surprisingly, we find during gas bladder development, Nkx2.1 and Sox2 expression are inconsistent with the hypothesis that they regulate the direction of gas bladder budding. Bmp4 is expressed ventrally during lung development in bichir, akin to the pattern during mouse lung development. During gas bladder development, Bmp4 is not expressed. However, Bmp16, a paralogue of Bmp4, is expressed dorsally in the developing gas bladder of bowfin. Bmp16 is present in the known genomes of Actinopteri (ray‐finned fishes excluding bichir) but absent from mammalian genomes. We hypothesize that Bmp16 was recruited to regulate gas bladder development in the Actinopteri in place of Bmp4. 相似文献
98.
J. Boone Kauffman Leila Giovanonni James Kelly Nicholas Dunstan Amy Borde Heida Diefenderfer Craig Cornu Christopher Janousek Jude Apple Laura Brophy 《Global Change Biology》2020,26(10):5679-5692
The coastal ecosystems of temperate North America provide a variety of ecosystem services including high rates of carbon sequestration. Yet, little data exist for the carbon stocks of major tidal wetland types in the Pacific Northwest, United States. We quantified the total ecosystem carbon stocks (TECS) in seagrass, emergent marshes, and forested tidal wetlands, occurring along increasing elevation and decreasing salinity gradients. The TECS included the total aboveground carbon stocks and the entire soil profile (to as deep as 3 m). TECS significantly increased along the elevation and salinity gradients: 217 ± 60 Mg C/ha for seagrass (low elevation/high salinity), 417 ± 70 Mg C/ha for low marsh, 551 ± 47 Mg C/ha for high marsh, and 1,064 ± 38 Mg C/ha for tidal forest (high elevation/low salinity). Soil carbon stocks accounted for >98% of TECS in the seagrass and marsh communities and 78% in the tidal forest. Soils in the 0–100 cm portion of the profile accounted for only 48%–53% of the TECS in seagrasses and marshes and 34% of the TECS in tidal forests. Thus, the commonly applied limit defining TECS to a 100 cm depth would greatly underestimate both carbon stocks and potential greenhouse gas emissions from land‐use conversion. The large carbon stocks coupled with other ecosystem services suggest value in the conservation and restoration of temperate zone tidal wetlands through climate change mitigation strategies. However, the findings suggest that long‐term sea‐level rise effects such as tidal inundation and increased porewater salinity will likely decrease ecosystem carbon stocks in the absence of upslope wetland migration buffer zones. 相似文献
99.
Yakuba M. Bah Jusufu Paye Mohamed S. Bah Abdulai Conteh Victoria Redwood-Sawyerr Mustapha Sonnie Amy Veinoglou Joseph B. Koroma Mary H. Hodges Yaobi Zhang 《PLoS neglected tropical diseases》2020,14(12)
BackgroundLymphatic filariasis (LF) is targeted for elimination in Sierra Leone. Epidemiological coverage of mass drug administration (MDA) with ivermectin and albendazole had been reported >65% in all 12 districts annually. Eight districts qualified to implement transmission assessment survey (TAS) in 2013 but were deferred until 2017 due to the Ebola outbreak (2014–2016). In 2017, four districts qualified for conducting a repeat pre-TAS after completing three more rounds of MDA and the final two districts were also eligible to implement a pre-TAS.Methodology/Principal findingsFor TAS, eight districts were surveyed as four evaluation units (EU). A school-based survey was conducted in children aged 6–7 years from 30 clusters per EU. For pre-TAS, one sentinel and one spot check site per district (with 2 spot check sites in Bombali) were selected and 300–350 persons aged 5 years and above were selected. For both surveys, finger prick blood samples were tested using the Filariasis Test Strips (FTS).For TAS, 7,143 children aged 6–7 years were surveyed across four EUs, and positives were found in three EUs, all below the critical cut-off value for each EU. For the repeat pre-TAS/pre-TAS, 3,994 persons over five years of age were surveyed. The Western Area Urban had FTS prevalence of 0.7% in two sites and qualified for TAS, while other five districts had sites with antigenemia prevalence >2%: 9.1–25.9% in Bombali, 7.5–19.4% in Koinadugu, 6.1–2.9% in Kailahun, 1.3–2.3% in Kenema and 1.7% - 3.7% in Western Area Rural.Conclusions/SignificanceEight districts in Sierra Leone have successfully passed TAS1 and stopped MDA, with one more district qualified for conducting TAS1, a significant progress towards LF elimination. However, great challenges exist in eliminating LF from the whole country with repeated failure of pre-TAS in border districts. Effort needs to be intensified to achieve LF elimination. 相似文献
100.
Joe Carver Domingos Ng Michelle Zhou Peggy Ko Dejin Zhan Mandy Yim David Shaw Brad Snedecor Michael W. Laird Steven Lang Amy Shen Zhilan Hu 《Biotechnology progress》2020,36(4):e2967
Historically, therapeutic protein production in Chinese hamster ovary (CHO) cells has been accomplished by random integration (RI) of expression plasmids into the host cell genome. More recently, the development of targeted integration (TI) host cells has allowed for recombination of plasmid DNA into a predetermined genomic locus, eliminating one contributor to clone-to-clone variability. In this study, a TI host capable of simultaneously integrating two plasmids at the same genomic site was used to assess the effect of antibody heavy chain and light chain gene dosage on antibody productivity. Our results showed that increasing antibody gene copy number can increase specific productivity, but with diminishing returns as more antibody genes are added to the same TI locus. Random integration of additional antibody DNA copies in to a targeted integration cell line showed a further increase in specific productivity, suggesting that targeting additional genomic sites for gene integration may be beneficial. Additionally, the position of antibody genes in the two plasmids was observed to have a strong effect on antibody expression level. These findings shed light on vector design to maximize production of conventional antibodies or tune expression for proper assembly of complex or bispecific antibodies in a TI system. 相似文献