全文获取类型
收费全文 | 236篇 |
免费 | 37篇 |
专业分类
273篇 |
出版年
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 3篇 |
2020年 | 2篇 |
2019年 | 1篇 |
2018年 | 3篇 |
2017年 | 1篇 |
2016年 | 4篇 |
2015年 | 6篇 |
2014年 | 10篇 |
2013年 | 8篇 |
2012年 | 16篇 |
2011年 | 15篇 |
2010年 | 13篇 |
2009年 | 10篇 |
2008年 | 18篇 |
2007年 | 14篇 |
2006年 | 14篇 |
2005年 | 12篇 |
2004年 | 9篇 |
2003年 | 8篇 |
2002年 | 13篇 |
2001年 | 6篇 |
2000年 | 8篇 |
1999年 | 8篇 |
1998年 | 9篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1994年 | 5篇 |
1993年 | 4篇 |
1992年 | 5篇 |
1991年 | 5篇 |
1990年 | 1篇 |
1989年 | 5篇 |
1988年 | 7篇 |
1987年 | 1篇 |
1986年 | 4篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1968年 | 1篇 |
1966年 | 3篇 |
1965年 | 1篇 |
排序方式: 共有273条查询结果,搜索用时 15 毫秒
1.
P K Gregersen H Kao A Nunez-Roldan C K Hurley R W Karr J Silver 《Journal of immunology (Baltimore, Md. : 1950)》1988,141(4):1365-1368
We have analyzed DNA sequence polymorphisms of DQ alpha and DQ beta chains from three haplotypes from the DRw52 family: DR5 DQw1 (FPA, GM3106), DRw6 DQw1 (CB6B, 10w9060), and DRw6 DQw3 (AMALA, 10w9064). The results indicate that the DR5 DQw1 and DRw6 DQw1 haplotypes have arisen by recombination between the DR beta 1 and DQ alpha loci. This contrasts with our previous analysis of DR4 DQ"Wa", DR3 DQ"Wa", and DR7 DQw3 haplotypes, all of which appear to have arisen by virtue of recombination between DQ alpha and DQ beta. Thus, there appear to be at least two different sites where recombination has occurred within the DR and DQ subregions. These differing patterns of recombination were interpreted in the context of the three major family groups of class II haplotypes, the DRw53, DRw52, and DR1/2 haplotype families. The data indicate that haplotypes from these family groups tend to undergo recombination at different locations. We propose that these differences in site of recombination are a reflection of differences in the molecular organization of the haplotypes belonging to each family group. 相似文献
2.
3.
P Merryman J Silver P K Gregersen G Solomon R Winchester 《Journal of immunology (Baltimore, Md. : 1950)》1989,143(6):2068-2073
The association of the class II genes of the DRw10 haplotype from a cell line, NASC, initiated from a member of a well characterized family, was analyzed by sequencing cDNA clones corresponding to DR beta I, DQ alpha, and DQ beta genes. An identical haplotype was also identified in the Raji cell line. In addition to typing as DRw10 and DQw1 with HLA typing sera both, the NASC and Raji cell lines were shown to react strongly with the monoclonal antibodies 109d6 (specific for DRw10 beta 1 and DRw53 beta 2 gene products) and Genox 3.5.3 (specific for DQw1) and exhibited the restriction fragment length polymorphism indicative of a DRw10, DQw1 haplotype. The DR beta 1 gene corresponding to the DRw10 specificity was found to have a first domain sequence different from all other DR beta I genes. Sequence analysis of the 3'-untranslated region of this DR beta-chain gene showed a significant divergence from the 3' untranslated region of the DRw53 family of haplotypes and a lesser divergence from that of the DRw52 and DR1/DR2 families. The sequence of the DQ beta genes corresponding to the DQw1 specificity in the DRw10 haplotype was found to be identical to the DQ beta gene from a DR1, DQw1 haplotype. Surprisingly, however, the DQ alpha gene did not resemble other DQw1-like DQ alpha genes, but was identical in sequence to the DQ alpha gene found in DR4 haplotypes. The novel association of DQ alpha and DQ beta genes in the DRw10 haplotype revealed in these studies may result from a double recombinational event. More consequentially, these studies strongly suggest that the DQw1 specificity recognized by Genox 3.5.3 is determined by the DQ beta chain and is not affected by the DQ alpha-chain. 相似文献
4.
5.
Apparent kinetic constants (Km and Vmax values) were determined for human liver acyl-CoA: glycine acyltransferase (glycine-N-acylase) towards isobutyryl-CoA, 2-methyl butyryl-CoA, isovaleryl-CoA, butyryl-CoA, hexanoyl-CoA, octanoyl-CoA, and decanoyl-CoA. These acyl-CoA esters were selected because of their relevance to the human diseases with cellular accumulation of these esters, i.e., especially to metabolic defects in the acyl-CoA dehydrogenation steps of the branched-chain amino acids, lysine, 5-hydroxy lysine, tryptophan, and fatty acid oxidation pathways. With the acyl-CoA ester as the fixed substrate, the Km value for glycine ranged from 0.5 to 2.9 mole/liter, and with glycine as fixed substrate, the Km values for the acyl-CoA esters varied from 0.3 to 5.6 mmole/liter. It is concluded that the substrate concentration is decisive for the glycine conjugate formation and that the occurrence in urine of acylglycines reflects an intramitochondrial accumulation of the corresponding acyl-CoA ester. 相似文献
6.
Joan Thiesen Torben S. Christensen Thomas G. Kristensen Rikke D. Andersen Brit Brunoe Trine K. Gregersen Mikkel Thrane Bo P. Weidema 《The International Journal of Life Cycle Assessment》2008,13(2):104-114
Goal, Scope and Background Traditionally, comparative life cycle assessments (LCA) have not considered rebound effects, for instance in case of significant
price differences among the compared products. No justifications have been made for this delimitation in scope. This article
shows that price differences and the consequent effects of marginal consumer expenditure may influence the conclusions of
comparative LCA significantly. We also show that considerations about rebound effects of price differences can be included
in LCAs.
Methods The direct rebound effect of a price difference is marginal consumption. Based on statistical data on private consumption
in different income groups (Statistics Denmark 2005a, 2005b), the present article provides an estimate of how an average Danish
household will spend an additional 1 DKK for further consumer goods, when the household has gained money from choosing a cheaper
product alternative. The approach is to use marginal income changes and the following changes in consumption patterns as an
expression for marginal consumption. Secondly, the environmental impact potentials related to this marginal consumption are
estimated by the use of environmental impact intensity data from an IO-LCA database (Weidema et al. 2005). Finally, it is
discussed whether, and in which ways the conclusions of comparative LCAs can be affected by including the price difference
between product alternatives. This is elucidated in a case study of a comparative LCA screening of two different kinds of
Danish cheese products (Fricke et al. 2004).
Results Car purchase and driving, use and maintenance of dwelling, clothing purchase and insurance constitutes the largest percentages
of the marginal consumption. In a case study of two cheeses, the including the impact potentials related to the price difference
results in significant changes in the total impact potentials. Considering the relatively small price difference of the two
products, it is likely also to have a significant influence on the results of comparative LCAs more generally.
Discussion The influence of marginal consumption in comparative LCAs is relevant to consider in situations with large differences in
the price of the product alternatives being compared, and in situations with minor differences in the impact potentials related
to the alternatives. However, different uncertainties are linked to determining the pattern for marginal consumption and the
environmental impact potential related to this. These are first of all related to the method used, but also include inaccurate
data of consumption in households, aggregation and weighting of income groups, aggregation of product groups, estimation and
size of the price difference, and the general applicability of the results.
Conclusion Incorporating marginal consumption in consequential LCAs is possible in practice. In the case study used, including the rebound
effects of the price difference has a significant influence on the result of the comparative LCA, as the result for the impact
categories acidification and nutrient enrichment changes in favour of the expensive product.
Recommendations and Perspectives It is recommended that the rebound effects of price differences should be included more frequently in LCAs. In order to ensure
this, further research in marginal consumption and investment patterns and IO data for different countries or regions is required.
Furthermore, this study does not consider the economic distributional consequences of buying an expensive product instead
of a cheaper product (e.g. related to how the profit is spent by those who provided the product). It should also be noted,
that more expensive products not necessarily result in less consumption, as those who provided the product also will spend
the money they have earned from the sale. Ideally, these consequences should also be further investigated. Likewise, the development
of databases to include marginal consumption in PC-tools is needed. In general, considerations of marginal consumption would
favour expensive product alternatives, depending, however, on the type of consumer.
ESS-Submission Editor: Dr. David Hunkeler (david.hunkeler@aquaplustech.ch) 相似文献
7.
Atherosclerosis is the most frequent cause of death and severe chronic disability in North America and Europe. The atherosclerosis-prone apolipoprotein E (apoE)-deficient mice contain the entire spectrum of lesions observed during atherogenesis. Significant remodelling of the artery occurs in atherosclerosis. The aim was to study the remodelling of the zero-stress state of the aorta in apoE-deficient mice up to 56 weeks of age. Normal wild-type mice served as control groups. The mice were euthanised at ages 10, 28 and 56 weeks and tissue rings where excised from several locations along the aorta. The rings where photographed in the no-load state (without any external forces applied), then cut radially to obtain the zero-stress state and photographed again. The cross-sectional wall area and wall thickness increased over time in apoE-deficient mice compared to controls (P<0.001). The residual strains at the inner and outer surface varied as function of aortic location both in controls and apoE-deficient mice (P<0.001). From age 28 to age 56 weeks a gradual increase in positive strain at the outer surface and negative strain at the inner surface was found in the apoE-deficient mice when compared to age-matched control mice (P<0.001). Furthermore, the inner residual strain in the plaque location was significantly smaller than in the non-plaque location in the rings with atherosclerotic plaques (P<0.001). The change over time of the opening angle was especially pronounced in the aortic arch. The opening angle increased to app. 200 degrees in the aortic arch in apoE-deficient mice at 56 weeks of age whereas it in age-matched controls was app. 125 degrees. Correspondingly, atherosclerotic plaques were prominent in the apoE-deficient mice, especially at week 56 in the ascending aorta and the aortic arch. In conclusion, a pronounced remodelling of the biomechanical properties in aorta was found in apoE-deficient mice. The stress gradient across the vessel wall in the plaque region is likely larger in vivo due to the smaller residual strain in the plaque area. 相似文献
8.
Kenny EE Pe'er I Karban A Ozelius L Mitchell AA Ng SM Erazo M Ostrer H Abraham C Abreu MT Atzmon G Barzilai N Brant SR Bressman S Burns ER Chowers Y Clark LN Darvasi A Doheny D Duerr RH Eliakim R Giladi N Gregersen PK Hakonarson H Jones MR Marder K McGovern DP Mulle J Orr-Urtreger A Proctor DD Pulver A Rotter JI Silverberg MS Ullman T Warren ST Waterman M Zhang W Bergman A Mayer L Katz S Desnick RJ Cho JH Peter I 《PLoS genetics》2012,8(3):e1002559
Crohn''s disease (CD) is a complex disorder resulting from the interaction of intestinal microbiota with the host immune system in genetically susceptible individuals. The largest meta-analysis of genome-wide association to date identified 71 CD–susceptibility loci in individuals of European ancestry. An important epidemiological feature of CD is that it is 2–4 times more prevalent among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Europeans (NJ). To explore genetic variation associated with CD in AJs, we conducted a genome-wide association study (GWAS) by combining raw genotype data across 10 AJ cohorts consisting of 907 cases and 2,345 controls in the discovery stage, followed up by a replication study in 971 cases and 2,124 controls. We confirmed genome-wide significant associations of 9 known CD loci in AJs and replicated 3 additional loci with strong signal (p<5×10−6). Novel signals detected among AJs were mapped to chromosomes 5q21.1 (rs7705924, combined p = 2×10−8; combined odds ratio OR = 1.48), 2p15 (rs6545946, p = 7×10−9; OR = 1.16), 8q21.11 (rs12677663, p = 2×10−8; OR = 1.15), 10q26.3 (rs10734105, p = 3×10−8; OR = 1.27), and 11q12.1 (rs11229030, p = 8×10−9; OR = 1.15), implicating biologically plausible candidate genes, including RPL7, CPAMD8, PRG2, and PRG3. In all, the 16 replicated and newly discovered loci, in addition to the three coding NOD2 variants, accounted for 11.2% of the total genetic variance for CD risk in the AJ population. This study demonstrates the complementary value of genetic studies in the Ashkenazim. 相似文献
9.
Seldin MF Shigeta R Villoslada P Selmi C Tuomilehto J Silva G Belmont JW Klareskog L Gregersen PK 《PLoS genetics》2006,2(9):e143
Using a genome-wide single nucleotide polymorphism (SNP) panel, we observed population structure in a diverse group of Europeans and European Americans. Under a variety of conditions and tests, there is a consistent and reproducible distinction between “northern” and “southern” European population groups: most individual participants with southern European ancestry (Italian, Spanish, Portuguese, and Greek) have >85% membership in the “southern” population; and most northern, western, eastern, and central Europeans have >90% in the “northern” population group. Ashkenazi Jewish as well as Sephardic Jewish origin also showed >85% membership in the “southern” population, consistent with a later Mediterranean origin of these ethnic groups. Based on this work, we have developed a core set of informative SNP markers that can control for this partition in European population structure in a variety of clinical and genetic studies. 相似文献
10.
The aims of the study were to evaluate characteristics of spontaneous motility and of the ascending excitatory peristaltic reflex (AEPR) and intraluminal cross-sectional area in the isolated perfused porcine duodenum. The parameters were measured by an intraluminal catheter by use of the perfused side-hole technique and impedance planimetry. Respiratory parameters such as pH and oxygen consumption and the arterial perfusion pressure were monitored and did not vary significantly throughout the study time. Spontaneous motility was intense at the beginning but declined and disappeared within 45-90 min. It was abolished by atropine, epinephrine, and UK-14,304 (an alpha 2-adrenoceptor agonist). Secondary motility was evoked by intraluminal balloon distensions by raising the balloon pressure to 1.5 kPa for 1-min periods. Reproducible results regarding the AEPR, external balloon diameters to elicit the AEPR, and intraluminal cross-sectional area were obtained. The order of potency (pD2 values) for inhibition of the AEPR was the selective M3-receptor antagonist 4-DAMP greater than atropine greater than the selective M2-receptor antagonist AFDX-116 greater than the selective M1-receptor antagonist pirenzepine greater than hexamethonium. 4-DAMP was 16 and 29 times more potent than AFDX-116 (P less than 0.02) and pirenzepine (P less than 0.02). None of the drugs altered the intraluminal cross-sectional area during the balloon distensions. The model provides the opportunity for physiological and pharmacological studies of duodenal motility and duodenal cross-sectional area devoid of extrinsic neural and endocrine effects. The abolishment of the AEPR by atropine is caused by blockade of the M3-receptor in the porcine duodenum. 相似文献