全文获取类型
收费全文 | 394篇 |
免费 | 20篇 |
出版年
2022年 | 7篇 |
2021年 | 6篇 |
2020年 | 5篇 |
2018年 | 9篇 |
2017年 | 3篇 |
2016年 | 9篇 |
2015年 | 22篇 |
2014年 | 13篇 |
2013年 | 17篇 |
2012年 | 20篇 |
2011年 | 23篇 |
2010年 | 21篇 |
2009年 | 13篇 |
2008年 | 19篇 |
2007年 | 18篇 |
2006年 | 19篇 |
2005年 | 17篇 |
2004年 | 15篇 |
2003年 | 15篇 |
2002年 | 17篇 |
2001年 | 14篇 |
2000年 | 13篇 |
1999年 | 4篇 |
1998年 | 6篇 |
1997年 | 6篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 6篇 |
1993年 | 4篇 |
1992年 | 9篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 4篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 4篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1974年 | 2篇 |
1972年 | 4篇 |
1969年 | 3篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1966年 | 3篇 |
1965年 | 3篇 |
1959年 | 2篇 |
1934年 | 1篇 |
排序方式: 共有414条查询结果,搜索用时 15 毫秒
21.
Venkataraman P Sridhar M Dhanammal S Vijayababu MR Srinivasan N Arunakaran J 《The Journal of nutritional biochemistry》2004,15(10):608-613
The ability of zinc to retard oxidative processes has been recognized for many years. Polychlorinated biphenyls (PCBs) are persistent and bioaccumulative environmental toxicants. Previous study has indicated that PCBs can have deleterious effects, including oxidative stress, on various aspects of reproduction in male rats. The aim of this study was to determine the antioxidant role of zinc in PCB-exposed ventral prostate of albino rats. A group of 20 rats were treated with Aroclor 1254 (2 mg/kg body weight/day, i.p.) for 30 days. After the PCB treatment, 10 rats were treated as PCB control. The remaining 10 rats were given zinc (Zn SO(4)) (200 mg/kg body weight/day, p.o.) for 10 days. Ventral prostatic enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) were estimated in all the groups. Hydrogen peroxide (H(2)O(2)), lipid peroxidation (LPO) and ventral prostatic acid phosphatase (ACP) were also estimated. Serum hormonal profiles such as total tri-iodothyronine (T(3)), thyroxine (T(4)), thyroid stimulating hormone (TSH), testosterone, and estradiol were estimated. Ventral prostatic androgen and estrogen receptors, ventral prostatic zinc content, and serum zinc concentration were also quantified in all the groups. Antioxidant enzymes such as SOD, CAT, GPx, GST, and ACP were decreased while an increase in H(2)O(2) and LPO were observed in PCB-treated animals. Decreased serum total T(3), T(4), testosterone, estradiol and increased TSH were observed in PCB-exposed rats. Ventral prostatic androgen and estrogen receptors were also decreased significantly in PCB-exposed rats. Zinc administration restored to previous levels all parameters except ventral prostatic ACP. These results suggest that PCB induces oxidative stress in rat ventral prostate by decreasing the levels of antioxidant enzymes; the effects could be reversed by the administration of zinc. The adverse effect of PCBs (Aroclor 1254) and zinc on ventral prostate might be due to indirect action through hormonal regulation. 相似文献
22.
23.
Venkataraman S Wagner BA Jiang X Wang HP Schafer FQ Ritchie JM Patrick BC Oberley LW Buettner GR 《Free radical research》2004,38(10):1119-1132
It has been hypothesized that exposure of cells to hyperthermia results in an increased flux of reactive oxygen species (ROS), primarily superoxide anion radicals, and that increasing antioxidant enzyme levels will result in protection of cells from the toxicity of these ROS. In this study, the prostate cancer cell line, PC-3, and its manganese superoxide dismutase (MnSOD)-overexpressing clones were subjected to hyperthermia (43°C, 1 h). Increased expression of MnSOD increased the mitochondrial membrane potential (MMP). Hyperthermic exposure of PC-3 cells resulted in increased ROS production, as determined by aconitase inactivation, lipid peroxidation, and H2O2 formation with a reduction in cell survival. In contrast, PC-3 cells overexpressing MnSOD had less ROS production, less lipid peroxidation, and greater cell survival compared to PC-3 Wt cells. Since MnSOD removes superoxide, these results suggest that superoxide free radical or its reaction products are responsible for part of the cytotoxicity associated with hyperthermia and that MnSOD can reduce cellular injury and thereby enhance heat tolerance. 相似文献
24.
Watanabe R Funato K Venkataraman K Futerman AH Riezman H 《The Journal of biological chemistry》2002,277(51):49538-49544
Ongoing sphingolipid synthesis is specifically required in vivo for the endoplasmic reticulum (ER) to Golgi transport of glycosylphosphatidylinositol (GPI)-anchored proteins. However, the sphingolipid intermediates that are required for transport nor their role(s) have been identified. Using stereoisomers of dihydrosphingosine, together with specific inhibitors and a mutant defective for sphingolipid synthesis, we now show that ceramides and/or inositol sphingolipids are indispensable for GPI-anchored protein transport. Furthermore, in the absence of sphingolipid synthesis, a significant fraction of GPI-anchored proteins is no longer associated tightly with the ER membrane. The loose membrane association is neither because of the lack of a GPI-anchor nor because of prolonged ER retention of GPI-anchored proteins. These results indicate that ceramides and/or inositol sphingolipids are required to stabilize the association of GPI-anchored proteins with membranes. They could act either by direct involvement as membrane components or as substrates for the remodeling of GPI lipid moieties. 相似文献
25.
Until now, ROS-GC1 signal transduction system was thought to be exclusive to photoreceptors in the retina. Two recent reports, however, now show that this is not the case. In one, the ROS-GC1 signal transduction system has been identified and characterized in pinealocyte neurons. This signaling is modulated by norepinephrine. However, the response of the individual pinealocyte neuron to the norepinephrine signal depends on whether the GCAP1-linked (results in hyperpolarization) or S100-linked (results in depolarization) pathway is operational in the pinealocyte. The GCAP1-linked pathway results in hyperpolarization, while the S100-linked pathway, in depolarization. The two pathways are mutually exclusive. In the other report, the calcium-modulated ROS-GC1:GCAP1 signaling system has been discovered in mitral cells of the olfactory bulb. These findings raise the possibility that a common theme of calcium-modulated ROS-GC signaling may be utilized in a wide variety of neurosensory cells. This idea is also supported from evolutionary and functional perspectives. 相似文献
26.
James R Myette Zachary Shriver Jian Liu Ganesh Venkataraman Robert Rosenberg Ram Sasisekharan 《Biochemical and biophysical research communications》2002,290(4):1206-1213
Heparan sulfate (HS) glycosaminoglycans are a structurally diverse class of complex biomolecules that modulate many important events at the cell surface and within the extracellular matrix and whose structural heterogeneity derives largely from the sequence-specific N- and O-sulfations catalyzed by an extensive repertoire of sulfating enzymes. We have expressed the human heparan sulfate 3-OST-1 isoform in Escherichia coli and subsequently purified a soluble, active enzyme. To assess its functionality, we determined the kinetic parameters for the recombinant 3-O-sulfotransferase-1 using a radiochemical assay that directly measures the 3-O-sulfation of unlabeled bovine kidney heparan sulfate in vitro using [(35)S]PAPS as the sulfate donor. The apparent K(m) values measured were in the low micromolar range (K(HS)(m) = 4.3 microM; K(PAPS)(m) = 38.6 microM); V(max) values of 18 and 21 pmol sulfate/min/pmol of enzyme for HS and PAPS, respectively. These values were compared with kinetic parameters likewise measured for recombinant 3-OST-1 purified from baculovirus-infected sf9 cells. The two enzymes appear to modify heparan sulfate in vitro to roughly the same extent and with comparable specificities. The expression of 3-OST-1 in E. coli represents an important step in subsequent structure-function studies. 相似文献
27.
Kuang R Epp JB Ruan S Chong LS Venkataraman R Tu J He S Truong TM Groutas WC 《Bioorganic & medicinal chemistry》2000,8(5):1005-1016
A series of carboxylate derivatives based on the 1,2,5-thiadiazolidin-3-one 1,1 dioxide and isothiazolidin-3-one 1,1 dioxide scaffolds has been synthesized and the inhibitory profile of these compounds toward human leukocyte elastase (HLE), cathepsin G (Cat G) and proteinase 3 (PR 3) was then determined. Most of the compounds were found to be potent, time-dependent inhibitors of elastase, with some of the compounds exhibiting k(inact)/K1 values as high as 4,928,300 M(-1) s(-1). The inhibitory potency of carboxylate derivatives based on the 1,2,5-thiadiazolidin-3-one 1,1 dioxide platform was found to be influenced by both the pKa and the inherent structure of the leaving group. Proper selection of the primary specificity group (R(I)) was found to lead to selective inhibition of HLE over Cat G, however, those compounds that inhibited HLE also inhibited PR 3, albeit less efficiently. The predictable mode of binding of these compounds suggests that, among closely-related serine proteases, highly selective inhibitors of a particular serine protease can be fashioned by exploiting subtle differences in their S' subsites. This study has also demonstrated that the degradative action of elastase on elastin can be abrogated in the presence of inhibitor 17. 相似文献
28.
Kavita Venkataraman Luor Shyuan Maudrene Tan Dianne Carrol Tan Bautista Konstadina Griva Yasmin Laura Marie Zuniga Mohamed Amir Yung Seng Lee Jeannette Lee E. Shyong Tai Eric Yin Hao Khoo Hwee Lin Wee 《PloS one》2015,10(9)
Background
Emotional distress is an important dimension in diabetes, and several instruments have been developed to measure this aspect. The Problem Areas in Diabetes (PAID) scale is one such instrument which has demonstrated validity and reliability in Western populations, but its psychometric properties in Asian populations have not been examined.Methods
This was a secondary analysis of data from patients with Type 2 diabetes mellitus recruited through convenience sampling from a diabetes specialist outpatient clinic in Singapore. The following psychometric properties were assessed: Construct validity through confirmatory factor analysis (CFA) and Rasch analysis, concurrent validity through correlation with related scales (Kessler Psychological Distress Scale, Diabetes Health Profile—psychological distress, Audit of Diabetes Dependent Quality of Life), reliability through assessment of internal consistency and floor and ceiling effects, and sensitivity by estimating effect sizes for known clinical and social functioning groups.Results
203 patients with mean age of 45±12 years were analysed. None of the previously published model structures achieved a good fit on CFA. On Rasch analysis, four items showed poor fit and were removed. The abridged 16-item PAID mapped to a single latent trait, with a high degree of internal consistency (Cronbach ɑ 0.95), but significant floor effect (24.6% scoring at floor). Both 20-item and 16-item PAID scores were moderately correlated with scores of related scales, and sensitive to differences in clinical and social functioning groups, with large effect sizes for glycemic control and diabetes related complications, nephropathy and neuropathy.Conclusion
The abridged 16-item PAID measures a single latent trait of emotional distress due to diabetes whereas the 20-item PAID appears to measures more than one latent trait. However, both the 16-item and 20-item PAID versions are valid, reliable and sensitive for use among Singaporean patients with diabetes. 相似文献29.
Sachi Horibata Tommy V. Vo Venkataraman Subramanian Paul R. Thompson Scott A. Coonrod 《Journal of visualized experiments : JoVE》2015,(99)
Given the inherent difficulties in investigating the mechanisms of tumor progression in vivo, cell-based assays such as the soft agar colony formation assay (hereafter called soft agar assay), which measures the ability of cells to proliferate in semi-solid matrices, remain a hallmark of cancer research. A key advantage of this technique over conventional 2D monolayer or 3D spheroid cell culture assays is the close mimicry of the 3D cellular environment to that seen in vivo. Importantly, the soft agar assay also provides an ideal tool to rigorously test the effects of novel compounds or treatment conditions on cell proliferation and migration. Additionally, this assay enables the quantitative assessment of cell transformation potential within the context of genetic perturbations. We recently identified peptidylarginine deiminase 2 (PADI2) as a potential breast cancer biomarker and therapeutic target. Here we highlight the utility of the soft agar assay for preclinical anti-cancer studies by testing the effects of the PADI inhibitor, BB-Cl-amidine (BB-CLA), on the tumorigenicity of human ductal carcinoma in situ (MCF10DCIS) cells. 相似文献
30.
Anish George Raghav T. Bhatia Gill L. Buchanan Anne Whiteside Robert S. Moisey Stephen F. Beer Sudipta Chattopadhyay Thozhukat Sathyapalan Joseph John 《PloS one》2015,10(11)