全文获取类型
收费全文 | 2303篇 |
免费 | 224篇 |
国内免费 | 1篇 |
出版年
2023年 | 10篇 |
2022年 | 22篇 |
2021年 | 44篇 |
2020年 | 37篇 |
2019年 | 36篇 |
2018年 | 41篇 |
2017年 | 46篇 |
2016年 | 58篇 |
2015年 | 118篇 |
2014年 | 145篇 |
2013年 | 155篇 |
2012年 | 214篇 |
2011年 | 164篇 |
2010年 | 149篇 |
2009年 | 117篇 |
2008年 | 120篇 |
2007年 | 143篇 |
2006年 | 132篇 |
2005年 | 117篇 |
2004年 | 106篇 |
2003年 | 99篇 |
2002年 | 90篇 |
2001年 | 37篇 |
2000年 | 27篇 |
1999年 | 29篇 |
1998年 | 20篇 |
1997年 | 14篇 |
1996年 | 17篇 |
1995年 | 8篇 |
1994年 | 10篇 |
1993年 | 15篇 |
1992年 | 17篇 |
1991年 | 15篇 |
1990年 | 12篇 |
1989年 | 13篇 |
1988年 | 11篇 |
1987年 | 10篇 |
1986年 | 10篇 |
1985年 | 8篇 |
1984年 | 15篇 |
1983年 | 5篇 |
1982年 | 6篇 |
1981年 | 7篇 |
1980年 | 5篇 |
1979年 | 13篇 |
1977年 | 3篇 |
1974年 | 3篇 |
1973年 | 3篇 |
1971年 | 5篇 |
1967年 | 6篇 |
排序方式: 共有2528条查询结果,搜索用时 31 毫秒
71.
Julia Blümer Juliana Rey Leif Dehmelt Tomá? Mazel Yao-Wen Wu Philippe Bastiaens Roger S. Goody Aymelt Itzen 《The Journal of cell biology》2013,200(3):287-300
Eukaryotic cells critically depend on the correct regulation of intracellular vesicular trafficking to transport biological material. The Rab subfamily of small guanosine triphosphatases controls these processes by acting as a molecular on/off switch. To fulfill their function, active Rab proteins need to localize to intracellular membranes via posttranslationally attached geranylgeranyl lipids. Each member of the manifold Rab family localizes specifically to a distinct membrane, but it is unclear how this specific membrane recruitment is achieved. Here, we demonstrate that Rab-activating guanosine diphosphate/guanosine triphosphate exchange factors (GEFs) display the minimal targeting machinery for recruiting Rabs from the cytosol to the correct membrane using the Rab-GEF pairs Rab5A–Rabex-5, Rab1A-DrrA, and Rab8-Rabin8 as model systems. Specific mistargeting of Rabex-5/DrrA/Rabin8 to mitochondria led to catalytic recruitment of Rab5A/Rab1A/Rab8A in a time-dependent manner that required the catalytic activity of the GEF. Therefore, RabGEFs are major determinants for specific Rab membrane targeting. 相似文献
72.
Alessandra Podda Giovanni Checcucci Wafa Mouhaya Delphine Centeno Valerie Rofidal Renata Del Carratore François Luro Raphael Morillon Patrick Ollitrault Bianca Elena Maserti 《Journal of plant physiology》2013
To understand the genotypic variation of citrus to mild salt stress, a proteomic approach has been carried out in parallel on two citrus genotypes (‘Cleopatra’ and ‘Willow leaf’ mandarins), which differ for Na+ and Cl− accumulation, and their cognate autotetraploids (4×). Using two-dimensional electrophoresis approximately 910 protein spots were reproducibly detected in control and salt-stressed leaves of all genotypes. Among them, 44 protein spots showing significant variations at least in one genotype were subjected to mass spectrometry analysis for identification. Salt-responsive proteins were involved in several functions, including photosynthetic processes, ROS scavenging, stress defence, and signalling. Genotype factors affect the salt-responsive pattern, especially that of carbon metabolism. The no ion accumulator ‘Cleopatra’ mandarin genotype showed the highest number of salt-responsive proteins, and up-regulation of Calvin cycle-related proteins. Conversely the ion accumulator ‘Willow leaf’ mandarin showed high levels of several photorespiration-related enzymes. A common set of proteins (twelve spots) displayed higher levels in salt-stressed leaves of 2× and 4× ‘Cleopatra’ and 4× ‘Willow leaf’ mandarin. Interestingly, antioxidant enzymes and heat shock proteins showed higher constitutive levels in 4× ‘Cleopatra’ mandarin and 4× ‘Willow leaf’ mandarin compared with the cognate 2× genotype. This work provides for the first time information on the effect of 8 weeks of salt stress on citrus genotypes contrasting for ion accumulation and their cognate autotetraploids. Results underline that genetic factors have a predominant effect on the salt response, although a common stress response independent from genotype was also found. 相似文献
73.
Wenrong Yang Qin Ren Ya‐Na Wu Vanessa K. Morris Anthony A. Rey Filip Braet Ann H. Kwan Margaret Sunde 《Biopolymers》2013,99(1):84-94
Class I fungal hydrophobins are small surface‐active proteins that self‐assemble to form amphipathic monolayers composed of amyloid‐like rodlets. The monolayers are extremely robust and can adsorb onto both hydrophobic and hydrophilic surfaces to reverse their wettability. This adherence is particularly strong for hydrophobic materials. In this report, we show that the class I hydrophobins EAS and HYD3 can self‐assemble to form a single‐molecule thick coating on a range of nanomaterials, including single‐walled carbon nanotubes (SWCNTs), graphene sheets, highly oriented pyrolytic graphite, and mica. Moreover, coating by class I hydrophobin results in a stable, dispersed preparation of SWCNTs in aqueous solutions. No cytotoxicity is detected when hydrophobin or hydrophobin‐coated SWCNTs are incubated with Caco‐2 cells in vitro. In addition, we are able to specifically introduce covalently linked chemical moieties to the hydrophilic side of the rodlet monolayer. Hence, class I hydrophobins provide a simple and effective strategy for controlling the surfaces of a range of materials at a molecular level and exhibit strong potential for biomedical applications. © 2012 Wiley Periodicals, Inc. 相似文献
74.
Masahito Kawano Rey IshiiYuki Yoshioka Takehito FukudaMinoru Tamura 《Archives of biochemistry and biophysics》2013
Noxa1 activates Nox2 together with Noxo1 and Rac in a pure reconstitution system, but the resulting activity is considerably lower than that induced by p67phox and p47phox. In this study, we found that C-terminal-truncated forms of Noxa1 exhibited higher activities than full-length Noxa1. Of the truncations examined, Noxa1(1-225) showed the highest ability for activation. Kinetic studies revealed that Noxa1(1-225) had a threefold higher Vmax value than full-length Noxa1 with a similar EC50 value. The affinities of Noxo1 and RacQ61L were not much altered by the truncation. Conversely, the affinity of FAD for the Nox2 complex was enhanced after the truncation. In the absence of Noxo1, Noxa1(1-225) showed much higher activity with a lower EC50 than full-length Noxa1. Noxa1(1-225) showed comparable activity to that of p67phox with either Noxo1 or p47phox, although the stability was lower than that with p67phox and p47phox. These findings indicate that the role of the C-terminal half of Noxa1 is autoinhibition. The data suggest a two-step autoinhibition mechanism, comprising self-masking to interrupt the binding to the oxidase, and holding of the activation domain in a suboptimal position to the oxidase. This study reveals that when both types of inhibition are released, Noxa1 achieves high-level superoxide production. 相似文献
75.
Christel Thauvin-Robinet Martine Auclair Laurence Duplomb Martine Caron-Debarle Magali Avila Judith St-Onge Martine Le?Merrer Bernard Le?Luyer Delphine Héron Michèle Mathieu-Dramard Pierre Bitoun Jean-Michel Petit Sylvie Odent Jeanne Amiel Damien Picot Virginie Carmignac Julien Thevenon Patrick Callier Martine Laville Yves Reznik Cédric Fagour Marie-Laure Nunes Jacqueline Capeau Olivier Lascols Frédéric Huet Laurence Faivre Corinne Vigouroux Jean-Baptiste Rivière 《American journal of human genetics》2013,93(1):141-149
Short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger anomaly, and teething delay (SHORT) syndrome is a developmental disorder with an unknown genetic cause and hallmarks that include insulin resistance and lack of subcutaneous fat. We ascertained two unrelated individuals with SHORT syndrome, hypothesized that the observed phenotype was most likely due to de novo mutations in the same gene, and performed whole-exome sequencing in the two probands and their unaffected parents. We then confirmed our initial observations in four other subjects with SHORT syndrome from three families, as well as 14 unrelated subjects presenting with syndromic insulin resistance and/or generalized lipoatrophy associated with dysmorphic features and growth retardation. Overall, we identified in nine affected individuals from eight families de novo or inherited PIK3R1 mutations, including a mutational hotspot (c.1945C>T [p.Arg649Trp]) present in four families. PIK3R1 encodes the p85α, p55α, and p50α regulatory subunits of class IA phosphatidylinositol 3 kinases (PI3Ks), which are known to play a key role in insulin signaling. Functional data from fibroblasts derived from individuals with PIK3R1 mutations showed severe insulin resistance for both proximal and distal PI3K-dependent signaling. Our findings extend the genetic causes of severe insulin-resistance syndromes and provide important information with respect to the function of PIK3R1 in normal development and its role in human diseases, including growth delay, Rieger anomaly and other ocular affections, insulin resistance, diabetes, paucity of fat, and ovarian cysts. 相似文献
76.
77.
Nikolaus E. Schultz Christopher E. Lane Line Le Gall Delphine Gey Anna R. Bigney Bruno De Reviers 《欧洲藻类学杂志》2013,48(4):481-500
In the western Atlantic Ocean, the brown algal genus Lobophora is currently represented by a single species, L. variegata, with a type locality designated by Lamouroux as ‘Antilles’. In this study, we used molecular-assisted alpha taxonomy (MAAT) to assess species diversity of Lobophora in Bermuda, the Florida Keys, St. Croix and Guadeloupe (Lesser Antilles). Using cox1 and cox3 sequences as barcode markers, five species of Lobophora, four of them novel, were delineated, all previously having been identified in the area as L. variegata. Our morphological and habitat studies, made possible by abundant sampling, have revealed unique characters for each of these western Atlantic species, including distinct cellular arrangements, as well as different depth ranges for certain species. Observations made from Lamouroux’s holotype of Dictyota variegata (= Lobophora variegata) allowed us to assess the anatomy of this species, which enabled us to easily align this early taxon to one of our genetic species from the western Atlantic. As the type was unavailable for genetic analysis, we selected a recent St. Croix (Virgin Is., Antilles) specimen as the epitype to support it with molecular sequence data. 相似文献
78.
Katherine E. Horn Stephen D. Glasgow Delphine Gobert Sarah-Jane Bull Tamarah Luk Jacklyn Girgis Marie-Eve Tremblay Danielle McEachern Jean-François Bouchard Michael Haber Edith Hamel Paul Krimpenfort Keith K. Murai Anton Berns Guy Doucet C. Andrew Chapman Edward S. Ruthazer Timothy E. Kennedy 《Cell reports》2013,3(1):173-185
- Download : Download full-size image
79.
Summary An extensive number of biochemical and physiological measurements were made over the third and fourth years of the growth of birch (Betula pendula Roth.) in elevated CO2. Trees in elevated CO2 had 58% more biomass than trees grown in ambient CO2 although relative growth rate was not affected in the last year of the study. No changes in biomass allocation were observed. Elevated CO2 caused an increase in starch accumulation in the leaves that resulted in a series of feedback mechanisms to re-establish the source-sink balance of the trees. A decrease in Rubisco activity and to a lesser extent in chlorophyll and soluble proteins led to a decrease in the photosynthetic activity. Although the positive CO 2effect on photosynthetic activity was maintained in the field over the whole experiment, the photosynthetic capacity of the trees was reduced by long-term exposure to elevated CO2. Both maximum electron transport capacity (J max) and maximum carboxylation capacity (V emax) were reduced to a similar extent, so the ratio of J max:V cmax was not altered. Root biomass, fine root density and mycorrhizal infection were increased in elevated CO 2. The mycorrhizal species of fungi associated with the trees grown in elevated CO2 were late-successional species whereas the species associated with trees grown in ambient CO2 were early successional species. This lends support to the hypothesis of a CO2 effect on the ontogeny of the trees. 相似文献
80.
Delphine Mirebeau-Prunier Soazig Le Pennec Caroline Jacques Jean-Fred Fontaine Naig Gueguen Nathalie Boutet-Bouzamondo Audrey Donnart Yves Malthièry Frédérique Savagner 《PloS one》2013,8(3)
Metabolic modifications of tumor cells are hallmarks of cancer. They exhibit an altered metabolism that allows them to sustain higher proliferation rates in hostile environment outside the cell. In thyroid tumors, the expression of the estrogen-related receptor α (ERRα), a major factor of metabolic adaptation, is closely related to the oxidative metabolism and the proliferative status of the cells. To elucidate the role played by ERRα in the glycolytic adaptation of tumor cells, we focused on the regulation of lactate dehydrogenases A and B (LDHA, LDHB) and the LDHA/LDHB ratio. Our study included tissue samples from 10 classical and 10 oncocytic variants of follicular thyroid tumors and 10 normal thyroid tissues, as well as samples from three human thyroid tumor cell lines: FTC-133, XTC.UC1 and RO82W-1. We identified multiple cis-acting promoter elements for ERRα, in both the LDHA and LDHB genes. The interaction between ERRα and LDH promoters was confirmed by chromatin immunoprecipitation assays and in vitro analysis for LDHB. Using knock-in and knock-out cellular models, we found an inverse correlation between ERRα expression and LDH activity. This suggests that thyroid tumor cells may reprogram their metabolic pathways through the up-regulation of ERRα by a process distinct from that proposed by the recently revisited Warburg hypothesis. 相似文献