全文获取类型
收费全文 | 1081篇 |
免费 | 27篇 |
国内免费 | 9篇 |
专业分类
系统科学 | 40篇 |
丛书文集 | 3篇 |
教育与普及 | 1篇 |
理论与方法论 | 19篇 |
现状及发展 | 579篇 |
研究方法 | 56篇 |
综合类 | 358篇 |
自然研究 | 61篇 |
出版年
2020年 | 15篇 |
2019年 | 8篇 |
2018年 | 25篇 |
2017年 | 24篇 |
2016年 | 32篇 |
2015年 | 28篇 |
2014年 | 24篇 |
2013年 | 26篇 |
2012年 | 39篇 |
2011年 | 68篇 |
2010年 | 29篇 |
2009年 | 12篇 |
2008年 | 35篇 |
2007年 | 37篇 |
2006年 | 31篇 |
2005年 | 27篇 |
2004年 | 27篇 |
2003年 | 36篇 |
2002年 | 30篇 |
2001年 | 22篇 |
2000年 | 20篇 |
1999年 | 20篇 |
1996年 | 18篇 |
1995年 | 12篇 |
1994年 | 12篇 |
1993年 | 14篇 |
1992年 | 15篇 |
1987年 | 8篇 |
1985年 | 8篇 |
1984年 | 12篇 |
1982年 | 10篇 |
1981年 | 12篇 |
1979年 | 24篇 |
1978年 | 18篇 |
1977年 | 21篇 |
1976年 | 19篇 |
1975年 | 14篇 |
1974年 | 17篇 |
1973年 | 21篇 |
1972年 | 15篇 |
1971年 | 17篇 |
1970年 | 25篇 |
1969年 | 20篇 |
1968年 | 20篇 |
1967年 | 17篇 |
1966年 | 13篇 |
1965年 | 8篇 |
1964年 | 10篇 |
1961年 | 9篇 |
1959年 | 7篇 |
排序方式: 共有1117条查询结果,搜索用时 15 毫秒
51.
Glaucia N. M. Hajj Camila P. Arantes Marcos Vinicios Salles Dias Martín Roffé Bruno Costa-Silva Marilene H. Lopes Isabel Porto-Carreiro Tatiana Rabachini Flávia R. Lima Flávio H. Beraldo Marco M. A. Prado Rafael Linden Vilma R. Martins 《Cellular and molecular life sciences : CMLS》2013,70(17):3211-3227
The co-chaperone stress-inducible protein 1 (STI1) is released by astrocytes, and has important neurotrophic properties upon binding to prion protein (PrPC). However, STI1 lacks a signal peptide and pharmacological approaches pointed that it does not follow a classical secretion mechanism. Ultracentrifugation, size exclusion chromatography, electron microscopy, vesicle labeling, and particle tracking analysis were used to identify three major types of extracellular vesicles (EVs) released from astrocytes with sizes ranging from 20–50, 100–200, and 300–400 nm. These EVs carry STI1 and present many exosomal markers, even though only a subpopulation had the typical exosomal morphology. The only protein, from those evaluated here, present exclusively in vesicles that have exosomal morphology was PrPC. STI1 partially co-localized with Rab5 and Rab7 in endosomal compartments, and a dominant-negative for vacuolar protein sorting 4A (VPS4A), required for formation of multivesicular bodies (MVBs), impaired EV and STI1 release. Flow cytometry and PK digestion demonstrated that STI1 localized to the outer leaflet of EVs, and its association with EVs greatly increased STI1 activity upon PrPC-dependent neuronal signaling. These results indicate that astrocytes secrete a diverse population of EVs derived from MVBs that contain STI1 and suggest that the interaction between EVs and neuronal surface components enhances STI1–PrPC signaling. 相似文献
52.
Lorena Beatriz Quiroga María Daniela Moreno Ariel Aníbal Cataldo Juan Héctor Aragón-Traverso María Victoria Pantano Juan Pablo Segundo Olivares 《Journal of Natural History》2015,49(27-28):1703-1716
The American bullfrog Lithobates catesbeianus has been introduced around the world, with invasive populations reported from almost all South American countries. A population of this species was introduced in the Calingasta department of San Juan province, which is an arid environment in western Argentina. This work provides information on the dietary composition of an invasive population of L. catesbeianus, and compares the degree of dietary overlap between adults and juveniles. Stomach contents of 169 bullfrogs (82 adults and 87 juveniles) were analysed. Adults consumed 40 prey taxa and Hymenoptera (Insecta) was the most numerous prey item (41.8%), followed by Araneae (13.6%) and Aeglidae (13.4%). Juveniles consumed 29 prey taxa and Hymenoptera constituted the highest percentage in prey number (77.2%). The trophic overlap niche index at the same level shows a value of 0.64 overlap in dietary community between adults and juveniles of this bullfrog. Aeglidae was volumetrically the most important trophic item (25.4%), followed by Anura (25.02%). Our results showed that cannibalism in bullfrogs is more common than the consumption of native anurans, coinciding with that reported in other populations of introduced bullfrogs. The high similarity in the diets of both size classes and the association between the size of the predator and prey suggest that the impact caused by bullfrogs throughout their ontogeny is high and probably has an impact on their prey. Freshwater crabs are the main items in the diet of Lithobates catesbeianus in other introduced populations and are usually the most conspicuous at our study site. The crabs in freshwater ecosystems are part of the lowest trophic level in the food chain. The major threats to the southern region’s freshwater crabs include deforestation, farming and exotic species. Lithobates catesbeianus has a generalist diet and high overlap between adults and juveniles. 相似文献
53.
Fatima-Zahra Idrissi María Isabel Geli 《Cellular and molecular life sciences : CMLS》2014,71(4):641-657
Endocytic budding implies the remodeling of a plasma membrane portion from a flat sheet to a closed vesicle. Clathrin- and actin-mediated endocytosis in yeast has proven a very powerful model to study this process, with more than 60 evolutionarily conserved proteins involved in fashioning primary endocytic vesicles. Major progress in the field has been made during the last decades by defining the sequential recruitment of the endocytic machinery at the cell cortex using live-cell fluorescence microscopy. Higher spatial resolution has been recently achieved by developing time-resolved electron microscopy methods, allowing for the first time the visualization of changes in the plasma membrane shape, coupled to the dynamics of the endocytic machinery. Here, we highlight these advances and review recent findings from yeast and mammals that have increased our understanding of where and how endocytic proteins may apply force to remodel the plasma membrane during different stages of the process. 相似文献
54.
55.
Coilín Boland Dianfan Li Syed Tasadaque Ali Shah Stefan Haberstock Volker Dötsch Frank Bernhard Martin Caffrey 《Cellular and molecular life sciences : CMLS》2014,71(24):4895-4910
Membrane proteins are key elements in cell physiology and drug targeting, but getting a high-resolution structure by crystallographic means is still enormously challenging. Novel strategies are in big demand to facilitate the structure determination process that will ultimately hasten the day when sequence information alone can provide a three-dimensional model. Cell-free or in vitro expression enables rapid access to large quantities of high-quality membrane proteins suitable for an array of applications. Despite its impressive efficiency, to date only two membrane proteins produced by the in vitro approach have yielded crystal structures. Here, we have analysed synergies of cell-free expression and crystallisation in lipid mesophases for generating an X-ray structure of the integral membrane enzyme diacylglycerol kinase to 2.28-Å resolution. The quality of cellular and cell-free-expressed kinase samples has been evaluated systematically by comparing (1) spectroscopic properties, (2) purity and oligomer formation, (3) lipid content and (4) functionality. DgkA is the first membrane enzyme crystallised based on cell-free expression. The study provides a basic standard for the crystallisation of cell-free-expressed membrane proteins and the methods detailed here should prove generally useful and contribute to accelerating the pace at which membrane protein structures are solved. 相似文献
56.
Wan J Yourshaw M Mamsa H Rudnik-Schöneborn S Menezes MP Hong JE Leong DW Senderek J Salman MS Chitayat D Seeman P von Moers A Graul-Neumann L Kornberg AJ Castro-Gago M Sobrido MJ Sanefuji M Shieh PB Salamon N Kim RC Vinters HV Chen Z Zerres K Ryan MM Nelson SF Jen JC 《Nature genetics》2012,44(6):704-708
RNA exosomes are multi-subunit complexes conserved throughout evolution and are emerging as the major cellular machinery for processing, surveillance and turnover of a diverse spectrum of coding and noncoding RNA substrates essential for viability. By exome sequencing, we discovered recessive mutations in EXOSC3 (encoding exosome component 3) in four siblings with infantile spinal motor neuron disease, cerebellar atrophy, progressive microcephaly and profound global developmental delay, consistent with pontocerebellar hypoplasia type 1 (PCH1; MIM 607596). We identified mutations in EXOSC3 in an additional 8 of 12 families with PCH1. Morpholino knockdown of exosc3 in zebrafish embryos caused embryonic maldevelopment, resulting in small brain size and poor motility, reminiscent of human clinical features, and these defects were largely rescued by co-injection with wild-type but not mutant exosc3 mRNA. These findings represent the first example of an RNA exosome core component gene that is responsible for a human disease and further implicate dysregulation of RNA processing in cerebellar and spinal motor neuron maldevelopment and degeneration. 相似文献
57.
S Peña-Llopis S Vega-Rubín-de-Celis A Liao N Leng A Pavía-Jiménez S Wang T Yamasaki L Zhrebker S Sivanand P Spence L Kinch T Hambuch S Jain Y Lotan V Margulis AI Sagalowsky PB Summerour W Kabbani SW Wong N Grishin M Laurent XJ Xie CD Haudenschild MT Ross DR Bentley P Kapur J Brugarolas 《Nature genetics》2012,44(9):1072
58.
59.
PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans
Grall A Guaguère E Planchais S Grond S Bourrat E Hausser I Hitte C Le Gallo M Derbois C Kim GJ Lagoutte L Degorce-Rubiales F Radner FP Thomas A Küry S Bensignor E Fontaine J Pin D Zimmermann R Zechner R Lathrop M Galibert F André C Fischer J 《Nature genetics》2012,44(2):140-147
Ichthyoses comprise a heterogeneous group of genodermatoses characterized by abnormal desquamation over the whole body, for which the genetic causes of several human forms remain unknown. We used a spontaneous dog model in the golden retriever breed, which is affected by a lamellar ichthyosis resembling human autosomal recessive congenital ichthyoses (ARCI), to carry out a genome-wide association study. We identified a homozygous insertion-deletion (indel) mutation in PNPLA1 that leads to a premature stop codon in all affected golden retriever dogs. We subsequently found one missense and one nonsense mutation in the catalytic domain of human PNPLA1 in six individuals with ARCI from two families. Further experiments highlighted the importance of PNPLA1 in the formation of the epidermal lipid barrier. This study identifies a new gene involved in human ichthyoses and provides insights into the localization and function of this yet uncharacterized member of the PNPLA protein family. 相似文献
60.
Oswaldo Hernández-Gallegos Felipe de Jesús Rodríguez-Romero Petra Sánchez-Nava Fausto R. Méndez 《西北部美国博物学家》2011,69(1)
Multiple surveys carried out by herpetologists in México, D.F., during the 1980s failed to find specimens of Aspidoscelis septemvitatta (Squamata: Teiidae). However, 10 specimens were recently collected to the east of México, D.F., inside a protected area, Sierra de Santa Catarina. The Sierra de Santa Catarina has been heavily modified by human activity and habitation. Morphological and natural history information about the specimens are presented, as well as notes on locality. 相似文献