全文获取类型
收费全文 | 1085篇 |
免费 | 191篇 |
出版年
2021年 | 14篇 |
2019年 | 9篇 |
2018年 | 9篇 |
2017年 | 10篇 |
2016年 | 20篇 |
2015年 | 34篇 |
2014年 | 34篇 |
2013年 | 37篇 |
2012年 | 46篇 |
2011年 | 54篇 |
2010年 | 32篇 |
2009年 | 40篇 |
2008年 | 35篇 |
2007年 | 43篇 |
2006年 | 58篇 |
2005年 | 39篇 |
2004年 | 41篇 |
2003年 | 49篇 |
2002年 | 35篇 |
2001年 | 28篇 |
2000年 | 37篇 |
1999年 | 22篇 |
1998年 | 23篇 |
1997年 | 13篇 |
1996年 | 13篇 |
1995年 | 10篇 |
1994年 | 14篇 |
1992年 | 24篇 |
1991年 | 28篇 |
1990年 | 20篇 |
1989年 | 14篇 |
1988年 | 23篇 |
1987年 | 20篇 |
1986年 | 19篇 |
1985年 | 22篇 |
1984年 | 14篇 |
1983年 | 15篇 |
1982年 | 15篇 |
1981年 | 14篇 |
1980年 | 11篇 |
1979年 | 22篇 |
1977年 | 14篇 |
1976年 | 11篇 |
1974年 | 12篇 |
1973年 | 25篇 |
1972年 | 18篇 |
1971年 | 8篇 |
1970年 | 8篇 |
1969年 | 10篇 |
1968年 | 11篇 |
排序方式: 共有1276条查询结果,搜索用时 31 毫秒
991.
Differential CD4+ T-lymphocyte apoptosis and bystander T-cell activation in rhesus macaques and sooty mangabeys during acute simian immunodeficiency virus infection
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Meythaler M Martinot A Wang Z Pryputniewicz S Kasheta M Ling B Marx PA O'Neil S Kaur A 《Journal of virology》2009,83(2):572-583
In contrast to pathogenic lentiviral infections, chronic simian immunodeficiency virus (SIV) infection in its natural host is characterized by a lack of increased immune activation and apoptosis. To determine whether these differences are species specific and predicted by the early host response to SIV in primary infection, we longitudinally examined T-lymphocyte apoptosis, immune activation, and the SIV-specific cellular immune response in experimentally infected rhesus macaques (RM) and sooty mangabeys (SM) with controlled or uncontrolled SIV infection. SIVsmE041, a primary SIVsm isolate, reproduced set-point viremia levels of natural SIV infection in SM but was controlled in RM, while SIVmac239 replicated to high levels in RM. Following SIV infection, increased CD8+ T-lymphocyte apoptosis, temporally coinciding with onset of SIV-specific cellular immunity, and elevated plasma Th1 cytokine and gamma interferon-induced chemokine levels were common to both SM and RM. Different from SM, SIV-infected RM showed a significantly higher frequency of peripheral blood activated CD8+ T lymphocytes despite comparable magnitude of the SIV-specific gamma interferon enzyme-linked immunospot response. Furthermore, an increase in CD4+ and CD4−CD8− T-lymphocyte apoptosis and plasma tumor necrosis factor-related apoptosis-inducing ligand were observed only in RM and occurred in both controlled SIVsmE041 and uncontrolled SIVmac239 infection. These data suggest that the “excess” activated T lymphocytes in RM soon after SIV infection are predominantly of non-virus-specific bystander origin. Thus, species-specific differences in the early innate immune response appear to be an important factor contributing to differential immune activation in natural and nonnatural hosts of SIV infection. 相似文献
992.
993.
994.
Changhao Bi Xueli Zhang Lonnie O. Ingram James F. Preston 《Applied and environmental microbiology》2009,75(18):5743-5749
Dilute acid pretreatment is an established method for hydrolyzing the methylglucuronoxylans of hemicellulose to release fermentable xylose. In addition to xylose, this process releases the aldouronate methylglucuronoxylose, which cannot be metabolized by current ethanologenic biocatalysts. Enterobacter asburiae JDR-1, isolated from colonized wood, was found to efficiently ferment both methylglucuronoxylose and xylose in acid hydrolysates of sweet gum xylan, producing predominantly ethanol and acetate. Transformation of E. asburiae JDR-1 with pLOI555 or pLOI297, each containing the PET operon containing pyruvate decarboxylase (pdc) and alcohol dehydrogenase B (adhB) genes derived from Zymomonas mobilis, replaced mixed-acid fermentation with homoethanol fermentation. Deletion of the pyruvate formate lyase (pflB) gene further increased the ethanol yield, resulting in a stable E. asburiae E1(pLOI555) strain that efficiently utilized both xylose and methylglucuronoxylose in dilute acid hydrolysates of sweet gum xylan. Ethanol was produced from xylan hydrolysate by E. asburiae E1(pLOI555) with a yield that was 99% of the theoretical maximum yield and at a rate of 0.11 g ethanol/g (dry weight) cells/h, which was 1.57 times the yield and 1.48 times the rate obtained with the ethanologenic strain Escherichia coli KO11. This engineered derivative of E. asburiae JDR-1 that is able to ferment the predominant hexoses and pentoses derived from both hemicellulose and cellulose fractions is a promising subject for development as an ethanologenic biocatalyst for production of fuels and chemicals from agricultural residues and energy crops.Lignocellulosic resources, including forest and agricultural residues and evolving energy crops, offer benign alternatives to petroleum-based resources for production of fuels and chemicals. As renewable resources, these lignocellulosic materials are expected to decrease dependence on exhaustible supplies of petroleum and mitigate the net release of carbon dioxide into the atmosphere. The development of economically acceptable bioconversion processes requires pretreatments that release the maximal quantities of hexoses (predominantly glucose released from cellulose) and pentoses (arabinose and xylose) from hemicelluloses and also requires microbial biocatalysts that efficiently convert these compounds to a single targeted product.As one of three main components of lignocellulosics, hemicellulose contains polysaccharides comprised of pentoses, hexoses and sugar acids that account for 20 to 35% of the total biomass from different sources (21). Methylglucuronoxylans (MeGAXn), consisting of long chains of as many as 70 β-xylopyranose residues linked by β-1,4-glycosidic bonds (25), are the predominant components in the hemicellulose fractions of agricultural residues and energy crops, including corn stover, sugarcane bagasse, poplar, and switchgrass (7, 18, 23, 24). In hardwood and softwood xylans, a 4-O-methylglucuronic acid is attached at the 2′ position of every sixth to eighth xylose residue (12, 15). Dilute acid hydrolysis is commonly used to make the monosaccharides comprising hemicellulose accessible for fermentation (7, 22). However, the α-1,2 glucuronosyl linkage in xylan is resistant to dilute acid hydrolysis, which results in the release of methylglucuronoxylose (MeGAX) along with xylose and other monosaccharides. MeGAX is not fermented by bacterial biocatalysts currently used to convert hemicellulose to ethanol, such as Escherichia coli KO11 (2, 6). In sweet gum xylan, as much as 27% of the carbohydrate may be in this unfermentable fraction after dilute acid pretreatment (2, 20). Complete utilization of all hemicellulosic sugars can improve the efficiency of conversion of lignocellulosic materials to fuel ethanol and other value-added products.Our previous research on the processing of hemicelluloses for fermentation led to isolation of Enterobacter asburiae strain JDR-1. This isolate performed mixed-acid fermentation of the principal hexoses and pentoses that can be derived from cellulose and hemicellulose fractions of lignocellulosic biomass and exhibited a novel metabolic potential based on its ability to ferment MeGAX and xylose to ethanol and acetate as major fermentation products from sweet gum MeGAXn hydrolysates generated by dilute acid pretreatment (2). This strain has been genetically modified to produce d-(−)-lactate as the predominant product from acid hydrolysates of MeGAXn (3).In this study, the PET operon containing the pdc, adhA, and adhB genes from Zymomonas mobilis (10, 11) was incorporated into a pflB E. asburiae JDR-1 isolate by plasmid transformation to construct homoethanologenic strains. The resulting recombinant strains were compared with E. asburiae wild-type strain JDR-1 and the ethanologenic strain E. coli KO11 to evaluate their efficiencies of production of ethanol from dilute acid hydrolysates of sweet gum MeGAXn. 相似文献
995.
Isabella Capellini Patrick McNamara Brian T. Preston Charles L. Nunn Robert A. Barton 《PloS one》2009,4(2)
Sleep is a pervasive characteristic of mammalian species, yet its purpose remains obscure. It is often proposed that ‘sleep is for the brain’, a view that is supported by experimental studies showing that sleep improves cognitive processes such as memory consolidation. Some comparative studies have also reported that mammalian sleep durations are higher among more encephalized species. However, no study has assessed the relationship between sleep and the brain structures that are implicated in specific cognitive processes across species. The hippocampus, neocortex and amygdala are important for memory consolidation and learning and are also in a highly actived state during sleep. We therefore investigated the evolutionary relationship between mammalian sleep and the size of these brain structures using phylogenetic comparative methods. We found that evolutionary increases in the size of the amygdala are associated with corresponding increases in NREM sleep durations. These results are consistent with the hypothesis that NREM sleep is functionally linked with specializations of the amygdala, including perhaps memory processing. 相似文献
996.
997.
Patricia Preston Lena Wartosch Dorothee G��nzel Michael Fromm Patthara Kongsuphol Jiraporn Ousingsawat Karl Kunzelmann Jacques Barhanin Richard Warth Thomas J. Jentsch 《The Journal of biological chemistry》2010,285(10):7165-7175
The KCNE3 β-subunit constitutively opens outwardly rectifying KCNQ1 (Kv7.1) K+ channels by abolishing their voltage-dependent gating. The resulting KCNQ1/KCNE3 heteromers display enhanced sensitivity to K+ channel inhibitors like chromanol 293B. KCNE3 was also suggested to modify biophysical properties of several other K+ channels, and a mutation in KCNE3 was proposed to underlie forms of human periodic paralysis. To investigate physiological roles of KCNE3, we now disrupted its gene in mice. kcne3−/− mice were viable and fertile and displayed neither periodic paralysis nor other obvious skeletal muscle abnormalities. KCNQ1/KCNE3 heteromers are present in basolateral membranes of intestinal and tracheal epithelial cells where they might facilitate transepithelial Cl− secretion through basolateral recycling of K+ ions and by increasing the electrochemical driving force for apical Cl− exit. Indeed, cAMP-stimulated electrogenic Cl− secretion across tracheal and intestinal epithelia was drastically reduced in kcne3−/− mice. Because the abundance and subcellular localization of KCNQ1 was unchanged in kcne3−/− mice, the modification of biophysical properties of KCNQ1 by KCNE3 is essential for its role in intestinal and tracheal transport. Further, these results suggest KCNE3 as a potential modifier gene in cystic fibrosis. 相似文献
998.
Emilie Combet Aziza El Mesmari Tom Preston Alan Crozier Kenneth E.L. McColl 《Free radical biology & medicine》2010,48(6):763-771
Acid-catalyzed nitrosation and production of potentially carcinogenic nitrosative species is focused at the gastroesophageal junction, where salivary nitrite, derived from dietary nitrate, encounters the gastric juice. Ascorbic acid provides protection by converting nitrosative species to nitric oxide (NO). However, NO may diffuse into adjacent lipid, where it reacts with O2 to re-form nitrosative species and N-nitrosocompounds (NOC). In this way, ascorbic acid promotes acid nitrosation. Using a novel benchtop model representing the gastroesophageal junction, this study aimed to clarify the action of a range of water-soluble antioxidants on the nitrosative mechanisms in the presence or absence of lipids. Caffeic, ferulic, gallic, or chlorogenic and ascorbic acids were added individually to simulated gastric juice containing secondary amines, with or without lipid. NO and O2 levels were monitored by electrochemical detection. NOC were measured in both aqueous and lipid phases by gas chromatography–tandem mass spectrometry. In the absence of lipids, all antioxidants tested inhibited nitrosation, ranging from 35.9 ± 7.4% with gallic acid to 93 ± 0.6% with ferulic acid. In the presence of lipids, the impact of each antioxidant on nitrosation was inversely correlated with the levels of NO they generated (R2 = 0.95, p < 0.01): gallic, chlorogenic, and ascorbic acid promoted nitrosation, whereas ferulic and caffeic acids markedly inhibited nitrosation. 相似文献
999.
A. C. Ronse Z. A. Popper J. C. Preston M. F. Watson 《Plant Systematics and Evolution》2010,287(1-2):1-17
European representatives of Apium sensu lato (Apiaceae), and Apium prostratum and Naufraga balearica, were studied with morphological, fruit anatomical, and palynological methods. Morphometric data were compared with phylogenetic results from previous molecular studies. This confirms that most of the European Apium species belong to a separate group corresponding to the previously named genus Helosciadium. All these species had previously been formally named as Helosciadium species, except for the new combination Helosciadium bermejoi, which is formally described here. Molecular studies place Apium prostratum and Naufraga balearica close to Apium graveolens, the type species of Apium. Our morphometric results show similarities of Naufraga with H. bermejoi, but fruit anatomy distinguishes it both from Helosciadium and from A. graveolens/prostratum. The placement of Cyclospermum leptophyllum in a separate genus is confirmed. Diagnostic keys to the genera and Helosciadium species, and an annotated checklist are given. 相似文献
1000.
John P. Reganold Preston K. Andrews Jennifer R. Reeve Lynne Carpenter-Boggs Christopher W. Schadt J. Richard Alldredge Carolyn F. Ross Neal M. Davies Jizhong Zhou 《PloS one》2010,5(9)