全文获取类型
收费全文 | 2945篇 |
免费 | 197篇 |
出版年
2024年 | 6篇 |
2023年 | 21篇 |
2022年 | 54篇 |
2021年 | 85篇 |
2020年 | 57篇 |
2019年 | 60篇 |
2018年 | 78篇 |
2017年 | 82篇 |
2016年 | 114篇 |
2015年 | 172篇 |
2014年 | 206篇 |
2013年 | 226篇 |
2012年 | 256篇 |
2011年 | 252篇 |
2010年 | 152篇 |
2009年 | 160篇 |
2008年 | 183篇 |
2007年 | 166篇 |
2006年 | 143篇 |
2005年 | 118篇 |
2004年 | 108篇 |
2003年 | 108篇 |
2002年 | 119篇 |
2001年 | 31篇 |
2000年 | 13篇 |
1999年 | 20篇 |
1998年 | 23篇 |
1997年 | 15篇 |
1996年 | 16篇 |
1995年 | 12篇 |
1994年 | 10篇 |
1993年 | 7篇 |
1992年 | 7篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1989年 | 5篇 |
1985年 | 4篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1977年 | 5篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1969年 | 2篇 |
1961年 | 3篇 |
排序方式: 共有3142条查询结果,搜索用时 15 毫秒
951.
Pat Whiteman Beatriz Hernandez de Madrid Paul Taylor Demin Li Rebecca Heslop Nattnee Viticheep Joyce Zi Tan Hideyuki Shimizu Juliana Callaghan Massimo Masiero Ji Liang Li Alison H. Banham Adrian L. Harris Susan M. Lea Christina Redfield Martin Baron Penny A. Handford 《The Journal of biological chemistry》2013,288(10):7305-7312
We have mapped a Jagged/Serrate-binding site to specific residues within the 12th EGF domain of human and Drosophila Notch. Two critical residues, involved in a hydrophobic interaction, provide a ligand-binding platform and are adjacent to a Fringe-sensitive residue that modulates Notch activity. Our data suggest that small variations within the binding site fine-tune ligand specificity, which may explain the observed sequence heterogeneity in mammalian Notch paralogues, and should allow the development of paralogue-specific ligand-blocking antibodies. As a proof of principle, we have generated a Notch-1-specific monoclonal antibody that blocks binding, thus paving the way for antibody tools for research and therapeutic applications. 相似文献
952.
Francesca Carella Noelia Carrasco Karl B. Andree Beatriz Lacuesta Dolors Furones Gionata De Vico 《Journal of invertebrate pathology》2013
In this work M. galloprovincialis and O. edulis specimens were surveyed for a pathological study in the Gulf of Naples (Mediterranean sea, Campania Region, southern Italy). Clusters of Nocardia sp.-like cells were observed in histological slides. PCR amplification, sequencing and in situ hybridization were carried out in order to corroborate Nocardia species identification for both hosts. Blast results showed a 99% of maximum identity with Nocardia crassostreae sequences in Genbank. This is the first report of N. crassostreae in the new host M. galloprovincialis and, in a new area, the Mediterranean Sea. 相似文献
953.
Irene Llorente‐Folch Ignasi Sahún Laura Contreras María José Casarejos Josep María Grau Takeyori Saheki María Angeles Mena Jorgina Satrústegui Mara Dierssen Beatriz Pardo 《Journal of neurochemistry》2013,124(3):347-362
The mitochondrial transporter of aspartate‐glutamate Aralar/AGC1 is a regulatory component of the malate‐aspartate shuttle. Aralar deficiency in mouse and human causes a shutdown of brain shuttle activity and global cerebral hypomyelination. A lack of neurofilament‐labeled processes is detected in the cerebral cortex, but whether different types of neurons are differentially affected by Aralar deficiency is still unknown. We have now found that Aralar‐knockout (Aralar‐KO) post‐natal mice show hyperactivity, anxiety‐like behavior, and hyperreactivity with a decrease of dopamine (DA) in terminal‐rich regions. The striatum is the brain region most affected in terms of size, amino acid and monoamine content. We find a decline in vesicular monoamine transporter‐2 (VMAT2) levels associated with increased DA metabolism through MAO activity (DOPAC/DA ratio) in Aralar‐KO striatum. However, no decrease in DA or in the number of nigral tyrosine hydroxylase‐positive cells was detected in Aralar‐KO brainstem. Adult Aralar‐hemizygous mice presented also increased DOPAC/DA ratio in striatum and enhanced sensitivity to amphetamine. Our results suggest that Aralar deficiency causes a fall in GSH/GSSG ratio and VMAT2 in striatum that might be related to a failure to produce mitochondrial NADH and to an increase of reactive oxygen species (ROS) in the cytosol. The results indicate that the nigrostriatal dopaminergic system is a target of Aralar deficiency. 相似文献
954.
955.
Beatriz Salgado Negret Fernanda Pérez Lars Markesteijn Mylthon Jiménez Castillo Juan J. Armesto 《Oecologia》2013,173(3):625-635
The study of functional traits and physiological mechanisms determining species’ drought tolerance is important for the prediction of their responses to climatic change. Fog-dependent forest patches in semiarid regions are a good study system with which to gain an understanding of species’ responses to increasing aridity and patch fragmentation. Here we measured leaf and hydraulic traits for three dominant species with contrasting distributions within patches in relict, fog-dependent forests in semiarid Chile. In addition, we assessed pressure–volume curve parameters in trees growing at a dry leeward edge and wet patch core. We predicted species would display contrasting suites of traits according to local water availability: from one end favoring water conservation and reducing cavitation risk, and from the opposite end favoring photosynthetic and hydraulic efficiency. Consistent with our hypothesis, we identified a continuum of water use strategies explaining species distribution along a small-scale moisture gradient. Drimys winteri, a tree restricted to the humid core, showed traits allowing efficient water transport and high carbon gain; in contrast, Myrceugenia correifolia, a tree that occurs in the drier patch edges, exhibited traits promoting water conservation and lower gas exchange rates, as well low water potential at turgor loss point. The most widespread species, Aextoxicon punctatum, showed intermediate trait values. Osmotic compensatory mechanism was detected in M. correifolia, but not in A. punctatum. We show that partitioning of the pronounced soil moisture gradients from patch cores to leeward edges among tree species is driven by differential drought tolerance. Such differences indicate that trees have contrasting abilities to cope with future reductions in soil moisture. 相似文献
956.
957.
Isidro Toro-Moyano Bienvenido Martínez-Navarro Jordi Agustí Caroline Souday José María Bermúdez de Castro María Martinón-Torres Beatriz Fajardo Mathieu Duval Christophe Falguères Oriol Oms Josep Maria Parés Pere Anadón Ramón Julià José Manuel García-Aguilar Anne-Marie Moigne María Patrocinio Espigares Sergio Ros-Montoya Paul Palmqvist 《Journal of human evolution》2013
The Orce region has one of the best late Pliocene and early Pleistocene continental paleobiological records of Europe. It is situated in the northeastern sector of the intramontane Guadix-Baza Basin (Granada, Andalusia, southern Spain). Here we describe a new fossil hominin tooth from the site of Barranco León, dated between 1.02 and 1.73 Ma (millions of years ago) by Electron Spin Resonance (ESR), which, in combination with paleomagnetic and biochronologic data, is estimated to be close to 1.4 Ma. While the range of dates obtained from these various methods overlaps with those published for the Sima del Elefante hominin locality (1.2 Ma), the overwhelming majority of evidence points to an older age. Thus, at the moment, the Barranco León hominin is the oldest from Western Europe. 相似文献
958.
The aims of this work were to investigate the microlocalisation of cadmium (Cd) in Lupinus albus L. cv. Multolupa nodules, and to determine its effects on carbon and nitrogen metabolism. Nodulated white lupin plants were grown in a growth chamber with or without Cd (150 μM). Energy-dispersive X-ray microanalysis showed the walls of the outer nodule cortex cells to be the main area of Cd retention, helping to reduce the harmful effect Cd might have on the amount of N2 fixed by the bacteroids. Sucrose synthase activity declined by 33% in the nodules of the Cd-treated plants, and smaller reductions were recorded in glutamine synthetase, aspartate aminotransferase, alkaline invertase and NADP-dependent isocitrate dehydrogenase activities. The Cd treatment also sharply reduced nodule concentrations of malate, succinate and citrate, while that of starch doubled, but that of sucrose experienced no significant change. In summary, the present results show that white lupins accumulate significant amounts of Cd in their root nodules. However, the activity of some enzymes involved in ammonium assimilation did decline, promoting a reduction in the plant N content. The downregulation of sucrose synthase limits the availability of carbon to the bacteroids, which might interfere with their respiration. Carbon metabolism therefore plays a primary role in the impaired function of the white lupin root nodule caused by Cd, while N metabolism appears to have a more secondary involvement. 相似文献
959.
Francisco J. Corpas Marina Leterrier Juan C. Begara-Morales Raquel Valderrama Mounira Chaki Javier López-Jaramillo Francisco Luque José M. Palma María N. Padilla Beatriz Sánchez-Calvo Capilla Mata-Pérez Juan B. Barroso 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Protein tyrosine nitration is a post-translational modification (PTM) mediated by nitric oxide-derived molecules. Peroxisomes are oxidative organelles in which the presence of nitric oxide (NO) has been reported.Methods
We studied peroxisomal nitroproteome of pea leaves by high-performance liquid chromatography with tandem mass spectrometry (LC–MS/MS) and proteomic approaches.Results
Proteomic analysis of peroxisomes from pea leaves detected a total of four nitro-tyrosine immunopositive proteins by using an antibody against nitrotyrosine. One of these proteins was found to be the NADH-dependent hydroxypyruvate reductase (HPR). The in vitro nitration of peroxisomal samples caused a 65% inhibition of HPR activity. Analysis of recombinant peroxisomal NADH-dependent HPR1 activity from Arabidopsis in the presence of H2O2, NO, GSH and peroxynitrite showed that the ONOO− molecule caused the highest inhibition of activity (51% at 5 mM SIN-1), with 5 mM H2O2 having no inhibitory effect. Mass spectrometric analysis of the nitrated recombinant HPR1 enabled us to determine that, among the eleven tyrosine present in this enzyme, only Tyr-97, Tyr-108 and Tyr-198 were exclusively nitrated to 3-nitrotyrosine by peroxynitrite. Site-directed mutagenesis confirmed Tyr198 as the primary site of nitration responsible for the inhibition on the enzymatic activity by peroxynitrite.Conclusion
These findings suggest that peroxisomal HPR is a target of peroxynitrite which provokes a loss of function.General significance
This is the first report demonstrating the peroxisomal NADH-dependent HPR activity involved in the photorespiration pathway is regulated by tyrosine nitration, indicating that peroxisomal NO metabolism may contribute to the regulation of physiological processes under no-stress conditions. 相似文献960.
Victor Camera Pimentel Daniela Zanini Andréia Machado Cardoso Roberta Schmatz Margarete Dulce Bagatini Jessié Martins Gutierres Fabiano Carvalho Jéssica Lopes Gomes Maribel Rubin Vera Maria Morsch Maria Beatriz Moretto Mariana Colino-Oliveira Ana Maria Sebastião Maria Rosa Chitolina Schetinger 《Neurochemical research》2013,38(4):886-894
It is well known that the levels of adenosine in the brain increase dramatically during cerebral hypoxic-ischemic (HI) insults. Its levels are tightly regulated by physiological and pathophysiological changes that occur during the injury acute phase. The aim of the present study was to examine the effects of the neonatal HI event on cytosolic and ecto-enzymes of purinergic system––NTPDase, 5′-nucleotidase (5′-NT) and adenosine deaminase (ADA)––in cerebral cortex of rats immediately post insult. Furthermore, the Na+/K+-ATPase activity, adenosine kinase (ADK) expression and thiobarbituric acid reactive species (TBARS) levels were assessed. Immediately after the HI event the cytosolic NTPDase and 5′-NT activities were increased in the cerebral cortex. In synaptosomes there was an increase in the ecto-ADA activity while the Na+/K+ ATPase activity presented a decrease. The difference between ATP, ADP, AMP and adenosine degradation in synaptosomal and cytosolic fractions could indicate that NTPDase, 5′-NT and ADA were differently affected after insult. Interestingly, no alterations in the ADK expression were observed. Furthermore, the Na+/K+-ATPase activity was correlated negatively with the cytosolic NTPDase activity and TBARS content. The increased hydrolysis of nucleotides ATP, ADP and AMP in the cytosol could contribute to increased adenosine levels, which could be related to a possible innate neuroprotective mechanism aiming at potentiating the ambient levels of adenosine. Together, these results may help the understanding of the mechanism by which adenosine is produced following neonatal HI injury, therefore highlighting putative therapeutical targets to minimize ischemic injury and enhance recovery. 相似文献