全文获取类型
收费全文 | 356篇 |
免费 | 44篇 |
出版年
2023年 | 2篇 |
2021年 | 4篇 |
2020年 | 5篇 |
2019年 | 3篇 |
2018年 | 5篇 |
2017年 | 8篇 |
2016年 | 8篇 |
2015年 | 13篇 |
2014年 | 12篇 |
2013年 | 9篇 |
2012年 | 28篇 |
2011年 | 23篇 |
2010年 | 14篇 |
2009年 | 11篇 |
2008年 | 22篇 |
2007年 | 16篇 |
2006年 | 8篇 |
2005年 | 12篇 |
2004年 | 12篇 |
2003年 | 10篇 |
2002年 | 16篇 |
2001年 | 10篇 |
2000年 | 9篇 |
1999年 | 4篇 |
1998年 | 9篇 |
1997年 | 9篇 |
1996年 | 11篇 |
1995年 | 7篇 |
1994年 | 9篇 |
1993年 | 5篇 |
1992年 | 7篇 |
1991年 | 6篇 |
1990年 | 2篇 |
1989年 | 8篇 |
1988年 | 8篇 |
1987年 | 4篇 |
1986年 | 7篇 |
1985年 | 6篇 |
1984年 | 4篇 |
1982年 | 3篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1973年 | 3篇 |
1968年 | 2篇 |
1930年 | 1篇 |
1929年 | 1篇 |
1905年 | 2篇 |
1890年 | 1篇 |
排序方式: 共有400条查询结果,搜索用时 31 毫秒
111.
Gudrun A. Brockmann Ersin Karatayli Christina Neuschl Ioannis M. Stylianou Soner Aksu Antje Ludwig Ulla Renne Chris S. Haley Sara Knott 《Mammalian genome》2007,18(11):757-766
An F2 pedigree based on the mouse lines DU6i and DBA/2 with extremely different growth and obesity characteristics was generated
to search for QTLs affecting serum concentrations of triglycerides (TG), total cholesterol (CHOL), HDL cholesterol (HDL-C),
and LDL cholesterol (LDL-C). Compared with many other studies, we searched for spontaneous genetic variants contributing to
high lipid levels under a standard breeding diet. Significant QTLs for CHOL were identified on chromosomes 4 and 6, and a
female-specific locus on chromosome 3. QTLs for HDL-C were detected on chromosome 11 for both sexes, and on chromosome 1 for
females. These QTLs are located in syntenic human regions that have QTLs that have not been previously confirmed in animal
studies. LDL-C QTLs have been mapped for both sexes to chromosome 8 and in males on chromosome 13. Epistatic interactions
that significantly accounted for the phenotypic variance of HDL-C, CHOL, and LDL-C serum concentrations were also detected
with one interaction between chromosomes 8 and 15, accounting for 22% of the observed variance in LDL-C levels. The identified
loci coincide in part with regions controlling growth and obesity. Thus, multiple genes or pleiotropic effects may be assumed.
The identified QTLs for cholesterol and its transport proteins as subcomponents of risk for coronary heart disease will further
improve our understanding of the genetic net controlling plasma lipid concentrations.
Electronic supplementary material The online version of this article (doi: ) contains supplementary material, which is available to authorized users. 相似文献
112.
113.
114.
115.
Loren B. Andreas Jan Stanek Tanguy Le Marchand Andrea Bertarello Diane Cala-De Paepe Daniela Lalli Magdaléna Krejčíková Camille Doyen Carl Öster Benno Knott Sebastian Wegner Frank Engelke Isabella C. Felli Roberta Pierattelli Nicholas E. Dixon Lyndon Emsley Torsten Herrmann Guido Pintacuda 《Journal of biomolecular NMR》2015,62(3):253-261
116.
Caenorhabditis elegans NONO‐1: Insights into DBHS protein structure,architecture, and function
下载免费PDF全文
![点击此处可从《Protein science : a publication of the Protein Society》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Gavin J. Knott Mihwa Lee Daniel M. Passon Archa H. Fox Charles S. Bond 《Protein science : a publication of the Protein Society》2015,24(12):2033-2043
Members of the Drosophila behavior/human splicing (DBHS) protein family have been characterized in the vertebrates Homo sapiens and Mus musculus, and the invertebrates Drosophila melanogaster and Chironomus tentans. Collectively, both vertebrate and invertebrate DBHS proteins function throughout gene regulation, largely but not always, within the nucleus. In this study, we report a structural and bioinformatic analysis of the DBHS protein family to guide future studies into DBHS protein function. To explore the structural plasticity of the family, we describe the 2.4 Å crystal structure of Caenorhabditis elegans non‐POU domain‐containing octamer‐binding protein 1 (NONO‐1). The structure is dimeric, with a domain arrangement consistent with mammalian DBHS proteins. Comparison with the DBHS structures available from H. sapiens reveals that there is inherent domain flexibility within the homologous DBHS region. Mapping amino acid similarity within the family to the NONO‐1 dimer highlights the dimer interface, coiled‐coil oligomerization motif, and putative RNA binding surfaces. Surprisingly, the interior surface of RNA recognition motif 2 (RRM2) that faces a large internal void is highly variable, but the external β2–β3 loops of RRM2 show remarkable preservation. Overall, the DBHS region is under strong purifying selection, whereas the sequences N‐ and C‐terminal to the DBHS region are less constrained. The findings described in this study provide a molecular basis for further investigation into the mechanistic function of the DBHS protein family in biology. 相似文献
117.
118.
Frederique M Moret Cornelis E Hack Kim MG van der Wurff-Jacobs Wilco de Jager Timothy RDJ Radstake Floris PJG Lafeber Joel AG van Roon 《Arthritis research & therapy》2013,15(5):R155
Introduction
Myeloid dendritic cells (mDCs) are potent T cell-activating antigen-presenting cells that have been suggested to play a crucial role in the regulation of immune responses in many disease states, including rheumatoid arthritis (RA). Despite this, studies that have reported on the capacity of naturally occurring circulating mDCs to regulate T cell activation in RA are still lacking. This study aimed to evaluate the phenotypic and functional properties of naturally occurring CD1c (BDCA-1)+ mDCs from synovial fluid (SF) compared to those from peripheral blood (PB) of RA patients.Methods
CD1c+ mDC numbers and expression of costimulatory molecules were assessed by fluorescence-activated cell sorting (FACS) analysis in SF and PB from RA patients. Ex vivo secretion of 45 inflammatory mediators by mDCs from SF and PB of RA patients was determined by multiplex immunoassay. The capacity of mDCs from SF to activate autologous CD4+ T cells was measured.Results
CD1c+ mDC numbers were significantly increased in SF versus PB of RA patients (mean 4.7% vs. 0.6%). mDCs from SF showed increased expression of antigen-presenting (human leukocyte antigen (HLA) class II, CD1c) and costimulatory molecules (CD80, CD86 and CD40). Numerous cytokines were equally abundantly produced by mDCs from both PB and SF (including IL-12, IL-23, IL-13, IL-21). SF mDCs secreted higher levels of interferon γ-inducible protein-10 (IP-10), monokine induced by interferon γ (MIG) and, thymus and activation-regulated chemokine (TARC), but lower macrophage-derived chemokine (MDC) levels compared to mDCs from PB. mDCs from SF displayed a strongly increased capacity to induce proliferation of CD4+ T cells associated with a strongly augmented IFNγ, IL-17, and IL-4 production.Conclusions
This study suggests that increased numbers of CD1c+ mDCs in SF are involved in the inflammatory cascade intra-articularly by the secretion of specific T cell-attracting chemokines and the activation of self-reactive T cells. 相似文献119.
E Taslidere N Vardi H Parlakpinar A Yıldız B Taslidere MG Karaaslan 《Biotechnic & histochemistry》2013,88(7):485-495
We evaluated the effects of melatonin on acetylsalicylic acid (ASA) induced gastroduodenal and jejunal mucosal injury. We used 40 postpubertal rats divided randomly into five groups of eight animals. The control group consisted of untreated animals. The Mel group was injected intraperitoneally (i.p.) with 5 mg/kg melatonin. The ASA group was injected i.p. with 200 mg/kg ASA. The ASA + Mel group was injected i.p. with 5 mg/kg melatonin 45 min after administering 200 mg/kg ASA i.p. The Mel + ASA group was injected i.p. with 5 mg/kg melatonin 45 min before administering 200 mg/kg ASA i.p. We found no statistically significant differences in mean histopathological scores in the ASA + Mel group compared to the ASA group. ASA caused shortened villi and loss of the apical villus in the duodenum. The histopathological score was increased and villus height was decreased in the ASA group compared to untreated controls. Treatment with melatonin attenuated the histological damage. In the ASA group, occasional areas showed erosion of villi in the jejunum; however, differences in mean histopathological score in ASA group compared to the other groups were not statistically significant. Malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) activities were measured in stomach, duodenal and jejunum tissue. We found increased MDA activity in both stomach and duodenal tissues in the ASA group compared to the control group (p < 0.05). We found no statistically significant changes in MDA levels in jejunal tissue in the ASA group compared to the control group. We found no change in SOD activity in either stomach or duodenal tissues in the ASA group compared to the control group. We observed decreased SOD activity in jejunal tissue in the ASA group compared to the control group (p < 0.05). We detected no change in GSH activity in stomach, duodenal or jejunal tissues in the ASA group compared to the control group. The stomach damage was less in melatonin treated groups, but the lesions were not completely eliminated. The jejunum in the ASA group retained a nearly normal appearance. We found that melatonin exhibited some healing effects on ASA induced duodenal mucosal injury. 相似文献
120.
Our understanding of how natural selection should shape sex allocation is perhaps more developed than for any other trait. However, this understanding is not matched by our knowledge of the genetic basis of sex allocation. Here, we examine the genetic basis of sex ratio variation in the parasitoid wasp Nasonia vitripennis, a species well known for its response to local mate competition (LMC). We identified a quantitative trait locus (QTL) for sex ratio on chromosome 2 and three weaker QTL on chromosomes 3 and 5. We tested predictions that genes associated with sex ratio should be pleiotropic for other traits by seeing if sex ratio QTL co-occurred with clutch size QTL. We found one clutch size QTL on chromosome 1, and six weaker QTL across chromosomes 2, 3 and 5, with some overlap to regions associated with sex ratio. The results suggest rather limited scope for pleiotropy between these traits. 相似文献