全文获取类型
收费全文 | 460篇 |
免费 | 19篇 |
专业分类
479篇 |
出版年
2022年 | 6篇 |
2021年 | 14篇 |
2020年 | 5篇 |
2019年 | 4篇 |
2018年 | 2篇 |
2016年 | 11篇 |
2015年 | 12篇 |
2014年 | 23篇 |
2013年 | 21篇 |
2012年 | 26篇 |
2011年 | 37篇 |
2010年 | 10篇 |
2009年 | 12篇 |
2008年 | 19篇 |
2007年 | 22篇 |
2006年 | 14篇 |
2005年 | 19篇 |
2004年 | 12篇 |
2003年 | 15篇 |
2002年 | 11篇 |
2001年 | 10篇 |
2000年 | 18篇 |
1999年 | 10篇 |
1998年 | 6篇 |
1997年 | 11篇 |
1996年 | 6篇 |
1995年 | 6篇 |
1994年 | 3篇 |
1993年 | 4篇 |
1992年 | 14篇 |
1991年 | 7篇 |
1990年 | 5篇 |
1989年 | 8篇 |
1988年 | 9篇 |
1987年 | 7篇 |
1986年 | 2篇 |
1985年 | 4篇 |
1984年 | 3篇 |
1983年 | 5篇 |
1981年 | 5篇 |
1980年 | 6篇 |
1979年 | 4篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 4篇 |
1972年 | 6篇 |
1969年 | 3篇 |
1965年 | 2篇 |
排序方式: 共有479条查询结果,搜索用时 15 毫秒
61.
McKay A Leung BP McInnes IB Thomson NC Liew FY 《Journal of immunology (Baltimore, Md. : 1950)》2004,172(5):2903-2908
Statins, the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, are effective serum cholesterol-lowering agents in clinical practice, and they may also have anti-inflammatory properties. Asthma is characterized by chronic eosinophilic inflammation in the airways, which is thought to be regulated by the activity of T lymphocytes. We therefore examined the anti-inflammatory activity of simvastatin in a murine model of allergic asthma. In mice previously sensitized to OVA, simvastatin treatment, either orally or i.p., reduced the total inflammatory cell infiltrate and eosinophilia in bronchoalveolar lavage fluid in response to inhaled OVA challenge. Simvastatin therapy i.p. was also associated with a reduction in IL-4 and IL-5 levels in bronchoalveolar lavage fluid and, at higher doses, a histological reduction in inflammatory infiltrates in the lungs. OVA-induced IL-4, IL-5, IL-6, and IFN-gamma secretion was reduced in thoracic lymph node cultures from simvastatin-treated mice. Simvastatin treatment did not alter serum total IgE or OVA-specific IgG1 and IgG2a levels. These data demonstrate the therapeutic potential of statin-sensitive pathways in allergic airways disease. 相似文献
62.
Saranya Limkaisang James Henry Cunnington Liew Kon Wui Baharuddin Salleh Yukio Sato Rangsi Divarangkoon Wanwisa Fangfuk Chaiwat To-anun Susumu Takamatsu 《Mycoscience》2006,47(6):327-335
To investigate the phylogenetic relationships among the powdery mildew fungi of some economically important tropical trees
belonging to Oidium subgenus Pseudoidium, we conducted molecular phylogenetic analyses using 30 DNA sequences of the rDNA internal transcribed spacer (ITS) regions
and 26 sequences of the domains D1 and D2 of the 28S rDNA obtained from the powdery mildews on Hevea brasiliensis (para rubber tree), Anacardium occidentale (cashew), Bixa orellana, Citrus spp., Mangifera indica (mango), and Acacia spp. The results indicate that the powdery mildew fungi isolated from these tropical trees are closely related to one another.
These powdery mildews are also closely related to E. alphitoides (including Erysiphe sp. on Quercus phillyraeoides). Because of the obligate biotrophic nature of the powdery mildew fungi, the relationship between powdery mildews and their
host plants is conservative. However, the present study suggests that a particular powdery mildew species has expanded its
host ranges on a wide range of the tropical trees. This article also suggests that a powdery mildew fungus distributed in
temperate regions of the Northern Hemisphere expanded its host ranges onto tropical plants and may be a good example of how
geographical and host range expansion has occurred in the Erysiphales. 相似文献
63.
Schilthuizen M van Til A Salverda M Liew TS James SS bin Elahan B Vermeulen JJ 《Evolution; international journal of organic evolution》2006,60(9):1851-1858
Genetic divergence in geographically isolated populations is a prerequisite for allopatric speciation, one of the most common modes of speciation. In ecologically equivalent populations existing within a small, environmentally homogeneous area, an important role for environmentally neutral divergence is often found or inferred. We studied a species complex of conspicuously shaped Opisthostoma land snails on scattered limestone outcrops within a small area of lowland rainforest in Borneo. We used shell morphometrics, mitochondrial and nuclear DNA sequences, and marks of predation to study the factors involved in allopatric divergence. We found that a striking geographic divergence exists in shell morphology, which is partly associated with neutral genetic divergence. We also found geographic differentiation in the behavior of the snails' invertebrate predator and evidence of an evolutionary interaction between aspects of shell shape and predator behavior. Our study shows that adaptation to biotic aspects of the environment may play a more important role in allopatric speciation than previously suspected, even on a geographically very small scale. 相似文献
64.
Marchant J Cowper B Liu Y Lai L Pinzan C Marq JB Friedrich N Sawmynaden K Liew L Chai W Childs RA Saouros S Simpson P Roque Barreira MC Feizi T Soldati-Favre D Matthews S 《The Journal of biological chemistry》2012,287(20):16720-16733
Toxosplasma gondii is the model parasite of the phylum Apicomplexa, which contains numerous obligate intracellular parasites of medical and veterinary importance, including Eimeria, Sarcocystis, Cryptosporidium, Cyclospora, and Plasmodium species. Members of this phylum actively enter host cells by a multistep process with the help of microneme protein (MIC) complexes that play important roles in motility, host cell attachment, moving junction formation, and invasion. T. gondii (Tg)MIC1-4-6 complex is the most extensively investigated microneme complex, which contributes to host cell recognition and attachment via the action of TgMIC1, a sialic acid-binding adhesin. Here, we report the structure of TgMIC4 and reveal its carbohydrate-binding specificity to a variety of galactose-containing carbohydrate ligands. The lectin is composed of six apple domains in which the fifth domain displays a potent galactose-binding activity, and which is cleaved from the complex during parasite invasion. We propose that galactose recognition by TgMIC4 may compromise host protection from galectin-mediated activation of the host immune system. 相似文献
65.
Jukka Miettinen Aljosja Hooijer Chenghua Shi Daniel Tollenaar Ronald Vernimmen Soo Chin Liew Chris Malins Susan E. Page 《Global Change Biology Bioenergy》2012,4(6):908-918
Tropical peatlands cover over 25 Mha in Southeast Asia and are estimated to contain around 70 Gt of carbon. Peat swamp forest ecosystems are an important part of the region's natural resources supporting unique flora and fauna endemic to Southeast Asia. Over recent years, industrial plantation development on peatland, especially for oil palm cultivation, has created intense debate due to its potentially adverse social and environmental effects. The lack of objective up‐to‐date information on the extent of industrial plantations has complicated quantification of their regional and global environmental consequences, both in terms of loss of forest and biodiversity as well as increases in carbon emissions. Based on visual interpretation of high‐resolution (30 m) satellite images, we find that industrial plantations covered over 3.1 Mha (20%) of the peatlands of Peninsular Malaysia, Sumatra and Borneo in 2010, surpassing the area of Belgium and causing an annual carbon emission from peat decomposition of 230–310 Mt CO2e. The majority (62%) of the plantations were located on the island of Sumatra, and over two‐thirds (69%) of all industrial plantations were developed for oil palm cultivation, with the remainder mostly being Acacia plantations for paper pulp production. Historical analysis shows strong acceleration of plantation development in recent years: 70% of all industrial plantations have been established since 2000 and only 4% of the current plantation area existed in 1990. ‘Business‐as‐usual’ projections of future conversion rates, based on historical rates over the past two decades, indicate that 6–9 Mha of peatland in insular Southeast Asia may be converted to plantations by the year 2020, unless land use planning policies or markets for products change. This would increase the annual carbon emission to somewhere between 380 and 920 Mt CO2e by 2020 depending on water management practices and the extent of plantations. 相似文献
66.
LMO4 is a broadly expressed LIM-only protein that is involved in neural tube development and implicated in breast cancer.
Here we report backbone and side chain NMR assignments for an engineered intramolecular complex of the N-terminal LIM domain
from LMO4 tethered to residues 641–685 of C-terminal binding protein interacting protein (CtIP/RBBP8). 相似文献
67.
The aim of this study was to develop a taste-masked oral disintegrating film (ODF) containing donepezil, with fast disintegration
time and suitable mechanical strength, for the treatment of Alzheimer’s disease. Hydroxypropyl methylcellulose, corn starch,
polyethylene glycol, lactose monohydrate and crosspovidone served as the hydrophilic polymeric bases of the ODF. The uniformity,
in vitro disintegration time, drug release and the folding endurance of the ODF were examined. The in vitro results showed that 80% of donepezil hydrochloride was released within 5 minutes with mean disintegration time of 44 seconds.
The result of the film flexibility test showed that the number of folding time to crack the film was 40 times, an indication
of sufficient mechanical property for patient use. A single-dose, fasting, four-period, eight-treatment, double-blind study
involving 16 healthy adult volunteers was performed to evaluate the in situ disintegration time and palatability of ODF. Five parameters, namely taste, aftertaste, mouthfeel, ease of handling and acceptance
were evaluated. The mean in situ disintegration time of ODF was 49 seconds. ODF containing 7 mg of sucralose were more superior than saccharin and aspartame
in terms of taste, aftertaste, mouthfeel and acceptance. Furthermore, the ODF was stable for at least 6 months when stored
at 40°C and 75% relative humidity. 相似文献
68.
Background
Accumulated biological research outcomes show that biological functions do not depend on individual genes, but on complex gene networks. Microarray data are widely used to cluster genes according to their expression levels across experimental conditions. However, functionally related genes generally do not show coherent expression across all conditions since any given cellular process is active only under a subset of conditions. Biclustering finds gene clusters that have similar expression levels across a subset of conditions. This paper proposes a seed-based algorithm that identifies coherent genes in an exhaustive, but efficient manner.Methods
In order to find the biclusters in a gene expression dataset, we exhaustively select combinations of genes and conditions as seeds to create candidate bicluster tables. The tables have two columns (a) a gene set, and (b) the conditions on which the gene set have dissimilar expression levels to the seed. First, the genes with less than the maximum number of dissimilar conditions are identified and a table of these genes is created. Second, the rows that have the same dissimilar conditions are grouped together. Third, the table is sorted in ascending order based on the number of dissimilar conditions. Finally, beginning with the first row of the table, a test is run repeatedly to determine whether the cardinality of the gene set in the row is greater than the minimum threshold number of genes in a bicluster. If so, a bicluster is outputted and the corresponding row is removed from the table. Repeating this process, all biclusters in the table are systematically identified until the table becomes empty.Conclusions
This paper presents a novel biclustering algorithm for the identification of additive biclusters. Since it involves exhaustively testing combinations of genes and conditions, the additive biclusters can be found more readily. 相似文献69.
70.
McKimmie CS Fraser AR Hansell C Gutiérrez L Philipsen S Connell L Rot A Kurowska-Stolarska M Carreno P Pruenster M Chu CC Lombardi G Halsey C McInnes IB Liew FY Nibbs RJ Graham GJ 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(5):3353-3363
D6 scavenges inflammatory chemokines and is essential for the regulation of inflammatory and immune responses. Mechanisms explaining the cellular basis for D6 function have been based on D6 expression by lymphatic endothelial cells. In this study, we demonstrate that functional D6 is also expressed by murine and human hemopoietic cells and that this expression can be regulated by pro- and anti-inflammatory agents. D6 expression was highest in B cells and dendritic cells (DCs). In myeloid cells, LPS down-regulated expression, while TGF-beta up-regulated expression. Activation of T cells with anti-CD3 and soluble CD28 up-regulated mRNA expression 20-fold, while maturation of human macrophage and megakaryocyte precursors also up-regulated D6 expression. Competition assays demonstrated that chemokine uptake was D6 dependent in human leukocytes, whereas mouse D6-null cells failed to uptake and clear inflammatory chemokines. Furthermore, we present evidence indicating that D6 expression is GATA1 dependent, thus explaining D6 expression in myeloid progenitor cells, mast cells, megakaryocytes, and DCs. We propose a model for D6 function in which leukocytes, within inflamed sites, activate D6 expression and thus trigger resolution of inflammatory responses. Our data on D6 expression by circulating DCs and B cells also suggest alternative roles for D6, perhaps in the coordination of innate and adaptive immune responses. These data therefore alter our models of in vivo D6 function and suggest possible discrete, and novel, roles for D6 on lymphatic endothelial cells and leukocytes. 相似文献