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101.
Background
The anterior cruciate ligament rupture is a common injury which mainly affects young and active population. Faced to this problem, the development of synthetic structures for ligament reconstruction is increasing. The most recent researches focused on the development of biodegradable structures that could be functionalized to enhance host integration. This work describes the elaboration of different poly(ε-caprolactone) prototypes for the rat anterior cruciate ligament replacement in order to found the best design for further in vivo assays.Methods
According to the literature, it was decided to elaborate two different poly(ε-caprolactone) prototypes: a braided one and a free-fibers one. A chemical grafting of a bioactive polymer–poly(sodium styrene sulfonate) – was performed on both prototypes and mechanical and biological testing were assessed. Based on these results, one rat was implanted with the best prototype.Results
The mechanical and biological results demonstrated that the best prototype to implant was the poly(sodium styrene sulfonate)-grafted braided prototype. After one-month implantation, no inflammation was observable around the scar. The rat demonstrated good flexion and extension of the lower limb without any anterior drawer. The prototype was highly anchored to the bone. ESEM images of the explanted prototype showed the presence of cells and tissue ingrowth along and around the fibers.Conclusion
This work demonstrates the feasibility to implant a bioactive and biodegradable synthetic ligament in the rat model without any inflammation and with a good tissue anchoring at a short-term time. This will lead to an extensive in vivo assay. 相似文献102.
Sven Loebrich Elisa Clark Kristina Ladd Stefani Takahashi Anna Brousseau Seth Kitchener 《MABS-AUSTIN》2019,11(2):335-349
The extent and pattern of glycosylation on therapeutic antibodies can influence their circulatory half-life, engagement of effector functions, and immunogenicity, with direct consequences to efficacy and patient safety. Hence, controlling glycosylation patterns is central to any drug development program, yet poses a formidable challenge to the bio-manufacturing industry. Process changes, which can affect glycosylation patterns, range from manufacturing at different scales or sites, to switching production process mode, all the way to using alternative host cell lines. In the emerging space of biosimilars development, often times all of these aspects apply. Gaining a deep understanding of the direction and extent to which glycosylation quality attributes can be modulated is key for efficient fine-tuning of glycan profiles in a stage appropriate manner, but establishment of such platform knowledge is time consuming and resource intensive. Here we report an inexpensive and highly adaptable screening system for comprehensive modulation of glycans on antibodies expressed in CHO cells. We characterize 10 media additives in univariable studies and in combination, using a design of experiments approach to map the design space for tuning glycosylation profile attributes. We introduce a robust workflow that does not require automation, yet enables rapid process optimization. We demonstrate scalability across deep wells, shake flasks, AMBR-15 cell culture system, and 2 L single-use bioreactors. Further, we show that it is broadly applicable to different molecules and host cell lineages. This universal approach permits fine-tuned modulation of glycan product quality, reduces development costs, and enables agile implementation of process changes throughout the product lifecycle. 相似文献
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105.
ngela M. Ribeiro Lara Puetz Nicholas B. Pattinson Love Daln Yuan Deng Guojie Zhang Rute R. da Fonseca Ben Smit M. Thomas P. Gilbert 《Molecular ecology》2019,28(16):3709-3721
Arid environments provide ideal ground for investigating the mechanisms of adaptive evolution. High temperatures and low water availability are relentless stressors for many endotherms, including birds; yet birds persist in deserts. While physiological adaptation probably involves metabolic phenotypes, the underlying mechanisms (plasticity, genetics) are largely uncharacterized. To explore this, we took an intraspecific approach that focused on a species that is resident over a mesic to arid gradient, the Karoo scrub‐robin (Cercotrichas coryphaeus). Specifically, we integrated environmental (climatic and primary productivity), physiological (metabolic rates: a measure of energy expenditure), genotypic (genetic variation underlying the machinery of energy production) and microbiome (involved in processing food from where energy is retrieved) data, to infer the mechanism of physiological adaptation. We that found the variation in energetic physiology phenotypes and gut microbiome composition are associated with environmental features as well as with variation in genes underlying energy metabolic pathways. Specifically, we identified a small list of candidate adaptive genes, some of them with known ties to relevant physiology phenotypes. Together our results suggest that selective pressures on energetic physiology mediated by genes related to energy homeostasis and possibly microbiota composition may facilitate adaptation to local conditions and provide an explanation to the high avian intraspecific divergence observed in harsh environments. 相似文献
106.
Natural populations often exist in spatially diverse environments and may experience variation in the strength and targets of natural selection across their ranges. Drosophila provides an excellent opportunity to study the effects of spatially varying selection in natural populations, as both Drosophila melanogaster and Drosophila simulans live across a wide range of environments in North America. Here, we characterize patterns of variation in transposable elements (TEs) from six populations of D. melanogaster and nine populations of D. simulans sampled from multiple latitudes across North America. We find a nearly twofold excess of TEs in D. melanogaster relative to D. simulans, with this difference largely driven by TEs segregating at the lowest and highest allele frequencies. We find no effect of latitude on either total TE abundance or average TE allele frequencies in either species. Moreover, we show that, as a class of mutations, the most common patterns of TE variation do not coincide with the sampled latitudinal gradient, nor are they consistent with local adaptation acting on environmental differences found in the most extreme latitudes. We also do not find a cline in ancestry for North American D. melanogaster—for either TEs or single nucleotide polymorphisms—suggesting a limited role for demography in shaping patterns of TE variation. Though we find little evidence for widespread clinality among TEs in Drosophila, this does not necessarily imply a limited role for TEs in adaptation. We discuss the need for improved models of adaptation to large‐scale environmental heterogeneity, and how these might be applied to TEs. 相似文献
107.
Kenji Suetsugu Masahide Yamato Jun Matsubayashi Ichiro Tayasu 《Molecular ecology》2019,28(18):4290-4299
The majority of chlorophyllous orchids form mycorrhizal associations with so‐called rhizoctonia fungi, a phylogenetically heterogeneous assemblage of predominantly saprotrophic fungi in Ceratobasidiaceae, Tulasnellaceae, and Serendipitaceae. It is still a matter of debate whether adult orchids mainly associated with rhizoctonia species are partially mycoheterotrophic. Here, we investigated the nutritional modes of green and albino variants of Goodyera velutina, an orchid species considered to be mainly associated with Ceratobasidium spp., by measuring their 13C and 15N abundances, and by molecular barcoding of their mycorrhizal fungi. Molecular analysis revealed that both green and albino variants of G. velutina harbored a similar range of mycobionts, mainly saprotrophic Ceratobasidium spp., Tulasnella spp., and ectomycorrhizal Russula spp. In addition, stable isotope analysis revealed that albino variants were significantly enriched in 13C but not so greatly in 15N, suggesting that saprotrophic Ceratobasidium spp. and Tulasnella spp. are their main carbon source. However, in green variants, 13C levels were depleted and those of 15N were indistinguishable from the co‐occurring autotrophic plants. Therefore, we concluded that the albino G. velutina variants are fully mycoheterotrophic plants whose C derives mainly from saprotrophic rhizoctonia, while the green G. velutina variants are mainly autotrophic plants, at least at our study site, in spite of their additional associations with ectomycorrhizal fungi. This is the first report demonstrating that adult nonphotosynthetic albino variants can obtain their nutrition mainly from nonectomycorrhizal rhizoctonia. 相似文献
108.
The formation of ecotypes has been invoked as an important driver of postglacial biodiversity, because many species colonized heterogeneous habitats and experienced divergent selection. Ecotype formation has been predominantly studied in outcrossing taxa, while far less attention has been paid to the implications of mating system shifts. Here, we addressed whether substrate‐related ecotypes exist in selfing and outcrossing populations of Arabidopsis lyrata subsp. lyrata and whether the genomic footprint differs between mating systems. The North American subspecies colonized both rocky and sandy habitats during postglacial range expansion and shifted the mating system from predominantly outcrossing to predominantly selfing in a number of regions. We performed an association study on pooled whole‐genome sequence data of 20 selfing or outcrossing populations, which suggested genes involved in adaptation to substrate. Motivated by enriched gene ontology terms, we compared root growth between plants from the two substrates in a common environment and found that plants originating from sand grew roots faster and produced more side roots, independent of mating system. Furthermore, single nucleotide polymorphisms associated with substrate‐related ecotypes were more clustered among selfing populations. Our study provides evidence for substrate‐related ecotypes in A. lyrata and divergence in the genomic footprint between mating systems. The latter is the likely result of selfing populations having experienced divergent selection on larger genomic regions due to higher genome‐wide linkage disequilibrium. 相似文献
109.
Bastian Mechsner Dietrich Böse Fabian Hogenkamp Nadia Ledermann Rudolf Hartmann Kevin Bochinsky Wolfgang Frey Jörg Pietruszka 《Bioorganic & medicinal chemistry》2019,27(13):2991-2997
The development of the first enantioselective total synthesis of altersolanol N is reported. The decisive step of the synthesis is the enantioselective formation of the tetrahydroanthraquinone nucleus by a [4 + 2]-cycloaddition in high yield and with excellent diastereo- and enantioselectivity (>95:5 dr and 95:5 er). In addition, a demanding selective monoacetylation of the OH group at the C-2 position was achieved: an epoxide ring opening with the participation of a neighbouring acetyl group could be established. The route proved to be an efficient alternative to also access enantiomerically pure altersolanol A. 相似文献
110.
随着近期我国"一带一路"生态文明建设以及生态文明建设的提出与实施,生态类型丰富但自然环境脆弱的西北地区再度引发学界关注。历史上罗布泊地区作为陆上丝绸之路交通重要节点,在中外文明交往与民族融合进程中发挥着重大作用,但如今罗布泊干涸以及罗布泊地区生态环境恶化的现实促使学界对该区域的生态环境演变历史进行反思。为进一步了解当前罗布泊地区生态环境研究的整体概况、热点议题及学术前沿趋势,从自然环境与人文环境两大方面对近二十年来罗布泊地区生态环境研究做出阶段性总结,以期为后续深入探讨区域生态环境变化与社会文明演进互动提供参考。 相似文献