全文获取类型
收费全文 | 332篇 |
免费 | 31篇 |
国内免费 | 1篇 |
专业分类
364篇 |
出版年
2023年 | 4篇 |
2022年 | 6篇 |
2020年 | 5篇 |
2019年 | 7篇 |
2017年 | 3篇 |
2016年 | 7篇 |
2015年 | 17篇 |
2014年 | 14篇 |
2013年 | 14篇 |
2012年 | 15篇 |
2011年 | 13篇 |
2010年 | 11篇 |
2009年 | 7篇 |
2008年 | 15篇 |
2007年 | 10篇 |
2006年 | 15篇 |
2005年 | 14篇 |
2004年 | 18篇 |
2003年 | 7篇 |
2002年 | 7篇 |
2001年 | 5篇 |
2000年 | 8篇 |
1999年 | 9篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1992年 | 7篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1989年 | 8篇 |
1988年 | 3篇 |
1987年 | 9篇 |
1986年 | 8篇 |
1985年 | 3篇 |
1984年 | 4篇 |
1983年 | 4篇 |
1982年 | 6篇 |
1981年 | 6篇 |
1980年 | 3篇 |
1979年 | 6篇 |
1978年 | 6篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1972年 | 2篇 |
1971年 | 5篇 |
1970年 | 3篇 |
1969年 | 2篇 |
1964年 | 2篇 |
1951年 | 2篇 |
排序方式: 共有364条查询结果,搜索用时 0 毫秒
51.
Alcohol abuse produces a considerable burden of illness in the Canadian population. The diagnosis of alcohol dependence and withdrawal can be difficult, particularly in the setting of covert intake or comorbidity. Two validated scales, the CAGE questionnaire to screen for alcohol abuse and dependence and the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale to assess the severity of withdrawal, are valuable tools for clinicians to use on a regular basis. For the treatment of alcohol withdrawal, compelling anecdotal evidence supports the routine administration of thiamine, but not necessarily other vitamins. Phenytoin has not been shown to be superior to placebo for uncomplicated withdrawal seizures. Neuroleptics are not recommended for routine use. Sedation with benzodiazepines guided by the CIWA-Ar results is recommended. There is good evidence that the management of alcohol withdrawal can be improved with the routine use of the CIWA-Ar scale to assess severity, treatment with adequate doses of benzodiazepines and follow-up monitoring of patients in alcohol withdrawal. 相似文献
52.
Kumita JR Helmfors L Williams J Luheshi LM Menzer L Dumoulin M Lomas DA Crowther DC Dobson CM Brorsson AC 《FASEB journal》2012,26(1):192-202
We have created a Drosophila model of lysozyme amyloidosis to investigate the in vivo behavior of disease-associated variants. To achieve this objective, wild-type (WT) protein and the amyloidogenic variants F57I and D67H were expressed in Drosophila melanogaster using the UAS-gal4 system and both the ubiquitous and retinal expression drivers Act5C-gal4 and gmr-gal4. The nontransgenic w(1118) Drosophila line was used as a control throughout. We utilized ELISA experiments to probe lysozyme protein levels, scanning electron microscopy for eye phenotype classification, and immunohistochemistry to detect the unfolded protein response (UPR) activation. We observed that expressing the destabilized F57I and D67H lysozymes triggers UPR activation, resulting in degradation of these variants, whereas the WT lysozyme is secreted into the fly hemolymph. Indeed, the level of WT was up to 17 times more abundant than the variant proteins. In addition, the F57I variant gave rise to a significant disruption of the eye development, and this correlated to pronounced UPR activation. These results support the concept that the onset of familial amyloid disease is linked to an inability of the UPR to degrade completely the amyloidogenic lysozymes prior to secretion, resulting in secretion of these destabilized variants, thereby leading to deposition and associated organ damage. 相似文献
53.
AB Chang NC Cox J Purcell JM Marchant PJ Lewindon GJ Cleghorn LC Ee GD Withers MK Patrick J Faoagali 《Respiratory research》2005,6(1):1-5
Background and methods
Human metapneumovirus (hMPV) is a recently discovered respiratory virus associated with bronchiolitis, pneumonia, croup and exacerbations of asthma. Since respiratory viruses are frequently detected in patients with acute exacerbations of COPD (AE-COPD) it was our aim to investigate the frequency of hMPV detection in a prospective cohort of hospitalized patients with AE-COPD compared to patients with stable COPD and to smokers without by means of quantitative real-time RT-PCR.Results
We analysed nasal lavage and induced sputum of 130 patients with AE-COPD, 65 patients with stable COPD and 34 smokers without COPD. HMPV was detected in 3/130 (2.3%) AE-COPD patients with a mean of 6.5 × 105 viral copies/ml in nasal lavage and 1.88 × 105 viral copies/ml in induced sputum. It was not found in patients with stable COPD or smokers without COPD.Conclusion
HMPV is only found in a very small number of patients with AE-COPD. However it should be considered as a further possible viral trigger of AE-COPD because asymptomatic carriage is unlikely. 相似文献54.
55.
Shannon L. Pelini Audrey M. Maran Angus R. Chen Justine Kaseman Thomas W. Crowther 《PloS one》2015,10(8)
Forest floor food webs play pivotal roles in carbon cycling, but they are rarely considered in models of carbon fluxes, including soil carbon dioxide emissions (respiration), under climatic warming. The indirect effects of invertebrates on heterotrophic (microbial and invertebrate) respiration through interactions with microbial communities are significant and will be altered by warming. However, the interactive effects of invertebrates and warming on heterotrophic respiration in the field are poorly understood. In this study we combined field and common garden laboratory approaches to examine relationships between warming, forest floor food web structure, and heterotrophic respiration. We found that soil animals can overwhelm the effects of warming (to 5 degrees Celsius above ambient) on heterotrophic respiration. In particular, the presence of higher trophic levels and burrowing detritivores strongly determined heterotrophic respiration rates in temperate forest soils. These effects were, however, context-dependent, with greater effects in a lower-latitude site. Without isolating and including the significant impact of invertebrates, climate models will be incomplete, hindering well-informed policy decisions. 相似文献
56.
Ann-Christin Brorsson Gian Gaetano Tartaglia Giorgio Favrin David A. Lomas Michele Vendruscolo Damian C. Crowther Leila M. Luheshi 《Biophysical journal》2010,98(8):1677-1684
The extent to which proteins aggregate into distinct structures ranging from prefibrillar oligomers to amyloid fibrils is key to the pathogenesis of many age-related degenerative diseases. We describe here for the Alzheimer's disease-related amyloid β peptide (Aβ) an investigation of the sequence-based determinants of the balance between the formation of prefibrillar aggregates and amyloid fibrils. We show that by introducing single-point mutations, it is possible to convert the normally harmless Aβ40 peptide into a pathogenic species by increasing its relative propensity to form prefibrillar but not fibrillar aggregates, and, conversely, to abolish the pathogenicity of the highly neurotoxic E22G Aβ42 peptide by reducing its relative propensity to form prefibrillar species rather than mature fibrillar ones. This observation can be rationalized by the demonstration that whereas regions of the sequence of high aggregation propensity dominate the overall tendency to aggregate, regions with low intrinsic aggregation propensities exert significant control over the balance of the prefibrillar and fibrillar species formed, and therefore play a major role in determining the neurotoxicity of the Aβ peptide. 相似文献
57.
58.
WhileEscherichia coli is common as a commensal organism in the distal ileum and colon, the presence of colonization factors (CF) on pathogenic strains ofE. coli facilitates attachment of the organism to intestinal receptor molecules in a species- and tissue-specific fashion. After the initial adherence, colonization occurs, and the involvement of additional virulence determinants leads to illness. EnterotoxigenicE. coli (ETEC) is the most extensively studied of the five categories ofE. coli that cause diarrheal disease, and has the greatest impact on health worldwide. ETEC can be isolated from domestic animals and humans. The biochemistry, genetics, epidemiology, antigenic characteristics, and cell and receptor binding properties of ETEC have been extensively described. Another major category, enteropathogenicE. coli (EPEC), has virulence mechanisms, primarily effacement and cytoskeletal rearrangement of intestinal brush borders, that are distinct from ETEC. An EPEC CF receptor has been purified and characterized as a sialidated transmembrane glycoprotein complex directly attached to actin, thereby associating CF-binding with host-cell response. Three, additional categories ofE. coli diarrheal disease, their colonization factors and their host cell receptors are discussed. It appears that biofilms exist in the intestine in a manner similar to oral bacterial biofilms, and thatE. coli is part of these biofilms as both commensals and pathogens.Abbreviations CF
colonization factor
- CFA
Colonization Factor Antigen
- CS
coli-surface-associated antigen
- EAggEC
enteroaggregativeE. coli
- ECDD
E. coli diarrheal disease
- EHEC
enterohemorrhagicE. coli
- EIEC
enteroinvasiveE. coli
- EPEC
enteropathogenicE. coli
- ETEC
enterotoxigenicE. coli
- Gal
galactose
- GalNAc
N-acetyl galactosamine
- LT
heat-labile toxin
- NeuAc
N-acetyl neuraminic acid
- PCF
Putative colonization factor
- RBC
red blood cells
- SLT
Shiga-like toxin
- ST
heat-stable toxin 相似文献
59.
Olive oil history,production and by-product management 总被引:1,自引:0,他引:1
Iosif Emmanouil Kapellakis Konstantinos P. Tsagarakis John C. Crowther 《Reviews in Environmental Science and Biotechnology》2008,7(1):1-26
In this review paper, the history of the olive tree and the development of the main olive oil extraction systems employed
in the past are presented. Furthermore, the management techniques employed from antiquity until today for the treatment of
olive mill wastewater (OMW), which constitutes the most important by-product of olive oil production, are addressed and compared.
Reference is also made to global olive oil production, the environmental impacts of the uncontrolled disposal of OMW, and
to the legal framework concerning its management in the main olive oil producing countries. Other by-products of olive processing
are also discussed. 相似文献
60.
David M. Klein Marcus C. Harding Meghan K Crowther Nathan J. Cherrington 《Journal of biochemical and molecular toxicology》2017,31(8)
The epididymis relies on transporters for the secretion of nucleosides and influence the disposition of nucleoside analogs (NSA). Since these compounds can cross the blood–testis barrier (BTB), it is important to understand if the epididymis reabsorbs NSA drugs. The purpose of this study is to determine the localization of nucleoside transporters expressed within rat epididymis to demonstrate the potential of epididymal reabsorption. Using immunohistochemistry, we determined that equilibrative nucleoside transporter 1 (ENT1) is localized to the basolateral membrane of epithelial cells, ENT2 is expressed in the nucleus of the epithelium and CNT2 is expressed by basal cells. The expression pattern for these transporters suggests that nucleosides are able to access the epithelial cells of the epididymal duct via the blood, but not from the lumen. We did not find any evidence for a transepithelial reabsorption pathway indicating the NSA drugs that cross the BTB remain within the epididymis. 相似文献