全文获取类型
收费全文 | 741篇 |
免费 | 35篇 |
专业分类
776篇 |
出版年
2024年 | 1篇 |
2023年 | 10篇 |
2022年 | 28篇 |
2021年 | 43篇 |
2020年 | 19篇 |
2019年 | 32篇 |
2018年 | 34篇 |
2017年 | 24篇 |
2016年 | 41篇 |
2015年 | 47篇 |
2014年 | 46篇 |
2013年 | 68篇 |
2012年 | 61篇 |
2011年 | 62篇 |
2010年 | 29篇 |
2009年 | 27篇 |
2008年 | 31篇 |
2007年 | 30篇 |
2006年 | 39篇 |
2005年 | 26篇 |
2004年 | 18篇 |
2003年 | 18篇 |
2002年 | 9篇 |
2001年 | 3篇 |
2000年 | 4篇 |
1999年 | 3篇 |
1998年 | 2篇 |
1997年 | 4篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1990年 | 2篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有776条查询结果,搜索用时 0 毫秒
71.
72.
Mohamad Navab Arnab Chattopadhyay Greg Hough David Meriwether Spencer I. Fogelman Alan C. Wagner Victor Grijalva Feng Su G. M. Anantharamaiah Lin H. Hwang Kym F. Faull Srinivasa T. Reddy Alan M. Fogelman 《Journal of lipid research》2015,56(4):871-887
We previously reported that i) a Western diet increased levels of unsaturated lysophosphatidic acid (LPA) in small intestine and plasma of LDL receptor null (LDLR−/−) mice, and ii) supplementing standard mouse chow with unsaturated (but not saturated) LPA produced dyslipidemia and inflammation. Here we report that supplementing chow with unsaturated (but not saturated) LPA resulted in aortic atherosclerosis, which was ameliorated by adding transgenic 6F tomatoes. Supplementing chow with lysophosphatidylcholine (LysoPC) 18:1 (but not LysoPC 18:0) resulted in dyslipidemia similar to that seen on adding LPA 18:1 to chow. PF8380 (a specific inhibitor of autotaxin) significantly ameliorated the LysoPC 18:1-induced dyslipidemia. Supplementing chow with LysoPC 18:1 dramatically increased the levels of unsaturated LPA species in small intestine, liver, and plasma, and the increase was significantly ameliorated by PF8380 indicating that the conversion of LysoPC 18:1 to LPA 18:1 was autotaxin dependent. Adding LysoPC 18:0 to chow increased levels of LPA 18:0 in small intestine, liver, and plasma but was not altered by PF8380 indicating that conversion of LysoPC 18:0 to LPA 18:0 was autotaxin independent. We conclude that i) intestinally derived unsaturated (but not saturated) LPA can cause atherosclerosis in LDLR−/− mice, and ii) autotaxin mediates the conversion of unsaturated (but not saturated) LysoPC to LPA. 相似文献
73.
74.
75.
Yao YW Shi Y Jia ZF Jiang YH Gu Z Wang J Aljofan M Sun ZG 《Histochemistry and cell biology》2011,136(2):205-215
To investigate the biological significance of ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) involvement in oocyte maturation,
we screened for proteins that bound to UCH-L1 in mouse ovaries, and we found that the prostate tumor overexpressed-1 (PTOV1)
protein was able to bind to UCH-L1. PTOV1 is highly expressed in prostate cancers and considered as a potential marker for
carcinogenesis and the progress of prostate cancer. It was reported that PTOV1 plays an important role in cell cycle regulation,
but its role in mammalian oocyte development and meiosis is still unclear. In this paper, it was found that the expression
levels of PTOV1 in mouse ovaries progressively increased from prepubescence to adulthood. And we found by immunohistochemistry
that PTOV1 spreaded in both the cytoplasm and nuclei of oocytes during prepuberty, but in normal adult mouse oocytes, it concentrated
not only in nuclei but also on the plasma membrane, though in some oocytes with abnormal shapes, PTOV1 did not display the
typical distribution patterns. In granulosa cells, however, it was found to locate in the cytoplasm at all the selected ages.
In postnatal mouse ovaries (28 days), estradiol treatment induced the adult-specific distribution pattern of PTOV1 in oocytes.
In addition, UCH-L1 was shown to be associated with CDK1, which participated in the regulation of cell cycle and oocyte maturation.
Therefore, we propose that the distribution changes of PTOV1 are age-dependent, and significant for mouse oocyte development
and maturation. Moreover, the discovery that PTOV1 is associated with UCH-L1 in mouse oocytes supports the explanations for
that UCH-L1 is involved in oocyte development and maturation, especially under the regulation of estrogen. 相似文献
76.
Biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and characterisation of its blend with oil palm empty fruit bunch fibers 总被引:1,自引:0,他引:1
Poly(3-hydroxybutyrate-co-38 mol%-3-hydroxyvalerate) [P(3HB-co-38mol%-3HV)] was produced by Cupriavidus sp. USMAA2-4 in the presence of oleic acid and 1-pentanol. Due to enormous production of empty fruit bunch (EFB) in the oil palm plantation and high production cost of P(3HB-co-3HV), oil palm EFB fibers were used for biocomposites preparation. In this study, maleic anhydride (MA) and benzoyl peroxide (DBPO) were used to improve the miscibility between P(3HB-co-3HV) and EFB fibers. Introduction of MA into P(3HB-co-3HV) backbone reduced the molecular weight and improved the thermal stability of P(3HB-co-3HV). Thermal stability of P(3HB-co-3HV)/EFB composites was shown to be comparable to that of commercial packaging product. Composites with 35% EFB fibers content have the highest tensile strength compared to 30% and 40%. P(3HB-co-3HV)/EFB blends showed less chemicals leached compared to commercial packaging. 相似文献
77.
Serine Protease inhibitors (Serpins) like antithrombin, antitrypsin, neuroserpin, antichymotrypsin, protein C-inhibitor and plasminogen activator inhibitor is involved in important biological functions like blood coagulation, fibrinolysis, inflammation, cell migration and complement activation. Serpins native state is metastable, which undergoes transformation to a more stable state during the process of protease inhibition. Serpins are prone to conformation defects, however little is known about the factors and mechanisms which promote its conformational change and misfolding. Helix B region in serpins is with several point mutations which result in pathological conditions due to polymerization. Helix B analysis for residue burial and cavity was undertaken to understand its role in serpin structure function. A structural overlap and an accessible surface area analysis showed the deformation of strand 6B and exposure of helix B at N-terminal end in cleaved conformation but not in the native and latent conformation of various inhibitory serpins. A cleaved polymer like conformation of antitrypsin also showed deformation of s6B and helix B exposure. Cavity analysis showed that helix B residues were part of the largest cavity in most of the serpins in the native state which increase in size during the transformation to cleaved and latent states. These data for the first time show the importance of strand 6B deformation and exposure of helix B in smooth insertion of the reactive center loop during serpin inhibition and indicate that helix B exposure due to variants may increase its polymer propensity. ABBREVIATIONS: serpin -serine protease inhibitors RCL -reactive center loop ASA -accessible surface area. 相似文献
78.
Kralicek AV Radjainia M Mohamad Ali NA Carraher C Newcomb RD Mitra AK 《Protein expression and purification》2011,80(1):117-124
N-terminal fusion tags that enhance translation initiation or protein solubility are often used to facilitate protein overexpression. As the optimal tag for a given target protein cannot be predicted a priori, valuable time can be lost in cloning and manipulating the corresponding gene to generate different fusion constructs for expression analysis. We have developed a cell-free strategy that consolidates these steps, enabling the utility of a panel of nine fusion-tags to be determined within one to two days. This approach exploits the fact that PCR-amplified DNA can be used as a template for cell-free protein synthesis. Overlap/extension PCR using the TEV protease site as the overlap region allows the fusion of different T7 promoter (T7p)-tag-TEV DNA fragments with a TEV-gene-T7 terminator (T7ter) fragment. For tag sequences where the TEV site is not compatible, a short C?G? repeat (CGr) sequence can be used as the overlap region. The resulting T7p-tag-TEV-gene-T7ter constructs are then used as templates for PCR-directed cell-free protein synthesis to identify which tag-TEV-gene fusion protein produces the highest amount of soluble protein. We have successfully applied this approach to the overexpression of the Adiponectin hypervariable domain (AHD). Five of the nine N-terminal fusion tags tested enabled the synthesis of soluble recombinant protein. The best of these was the Peptidyl-prolylcis-trans isomerise B (PpiB) fusion tag which produces 1mg/ml amounts of soluble fusion protein. PpiB is an example of a new class of fusion tag known as the "stress-responsive proteins". Our results suggest that this cell-free fusion-tag expression screen facilitates the rapid identification of suitable fusion-tags that overcome issues such as poor expression and insolubility, often encountered using conventional approaches. 相似文献
79.
Nanyan?Noreen Wei?Yeng?Hooi Ali?Baradaran Mohamad?Rosfarizan Chin?Chin?Sieo Md?Illias?Rosli Khatijah?Yusoff Abdul?Rahim?RahaEmail author 《Microbial cell factories》2011,10(1):28
Background
Many plasmid-harbouring strains of Lactococcus lactis have been isolated from milk and other sources. Plasmids of Lactococcus have been shown to harbour antibiotic resistance genes and those that express some important proteins. The generally regarded as safe (GRAS) status of L. lactis also makes it an attractive host for the production of proteins that are beneficial in numerous applications such as the production of biopharmaceutical and nutraceutical. In the present work, strains of L. lactis were isolated from cow's milk, plasmids were isolated and characterised and one of the strains was identified as a potential new lactococcal host for the expression of heterologous proteins. 相似文献80.