全文获取类型
收费全文 | 104篇 |
免费 | 9篇 |
出版年
2023年 | 2篇 |
2022年 | 2篇 |
2020年 | 4篇 |
2019年 | 4篇 |
2018年 | 2篇 |
2017年 | 4篇 |
2016年 | 7篇 |
2015年 | 11篇 |
2014年 | 7篇 |
2013年 | 9篇 |
2012年 | 10篇 |
2011年 | 10篇 |
2010年 | 2篇 |
2009年 | 3篇 |
2008年 | 1篇 |
2007年 | 3篇 |
2006年 | 1篇 |
2005年 | 5篇 |
2004年 | 2篇 |
2003年 | 3篇 |
2002年 | 2篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1994年 | 3篇 |
1992年 | 1篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1985年 | 1篇 |
排序方式: 共有113条查询结果,搜索用时 31 毫秒
51.
Ulett GC Maclean KH Nekkalapu S Cleveland JL Adderson EE 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(4):2555-2562
Apoptosis of murine and human macrophages induced by group B Streptococcus agalactiae (GBS) is likely an important virulence mechanism that is used by the bacteria to suppress the host immune response and to persist at sites of infection. The mechanisms by which GBS induces apoptosis are, however, largely unknown. In this study, we report that in murine macrophages GBS induces unique changes in the regulation and localization of the apoptotic regulators Bad, 14-3-3, and Omi/high-temperature requirement A2 and leads to the release of cytochrome c and the activation of caspase-9 and caspase-3. Furthermore, inhibition of caspase-3 impaired GBS-induced apoptosis of macrophages. The ability to modulate the activity of effector caspases may therefore represent an unexploited avenue for therapeutic intervention in GBS infections. 相似文献
52.
M. Sebastin Santhosh M. Shanmuga Sundaram K. Sunitha S. Jnaneshwari S. Devaraja K. Kemparaju K. S. Girish 《Cytotechnology》2016,68(1):73-85
Viper envenomation results in inflammation at the bitten site as well as target organs. Neutrophils and other polymorphonuclear leukocytes execute inflammation resolving mechanism and will undergo apoptosis after completing the task. However, the target specific toxins induce neutrophil apoptosis at the bitten site and in circulation prior to their function, thus reducing their number. Circulating activated neutrophils are major source of inflammatory cytokines and leakage of reactive oxygen species (ROS)/other toxic intermediates resulting in aggravation of inflammatory response at the bitten/target site. Therefore, neutralization of venom induced neutrophil apoptosis reduces inflammation besides increasing the functional neutrophil population. Therefore, the present study investigates the venom induced perturbances in isolated human neutrophils and its neutralization by crocin (Crocus sativus) a potent antioxidant carotenoid. Human neutrophils on treatment with venom resulted in altered ROS generation, intracellular Ca2+ mobilization, mitochondrial membrane depolarization, cyt-c translocation, caspase activation, phosphatidylserine externalization and DNA damage. On the other hand significant protection against oxidative stress and apoptosis were evidenced in crocin pre-treated groups. In conclusion the viper venom induces neutrophil apoptosis and results in aggravation of inflammation and tissue damage. The present study demands the necessity of an auxiliary therapy in addition to antivenin therapy to treat secondary/overlooked complications of envenomation. 相似文献
53.
The medium for recombinant phytase production by E. coli BL21 was optimized using response surface methodology. A 23 central composite experimental design was used to study the combined effect of the medium components, tryptone, yeast extract and NaCl. Addition of 2?g/l glucose to the medium greatly influenced the phytase production. The optimization of the medium has increased the phytase production by 1.2 times. The incorporation of 2?g/l glucose significantly enhanced the phytase production by 1.58 times, showing an overall 2.78 fold increase before optimization and other modifications of the medium. The optimized medium with glucose showed a highest phytase activity of 2250?U/l. 相似文献
54.
Hieu Sy Vu Mary R. Roth Pamela Tamura Thilani Samarakoon Sunitha Shiva Samuel Honey Kaleb Lowe Eric A. Schmelz Todd D. Williams Ruth Welti 《Physiologia plantarum》2014,150(4):517-528
Formation of galactose‐acylated monogalactosyldiacylglycerols has been shown to be induced by leaf homogenization, mechanical wounding, avirulent bacterial infection and thawing after snap‐freezing. Here, lipidomic analysis using mass spectrometry showed that galactose‐acylated monogalactosyldiacylglycerols, formed in wheat (Triticum aestivum) and tomato (Solanum lycopersicum) leaves upon wounding, have acyl‐galactose profiles that differ from those of wounded Arabidopsis thaliana, indicating that different plant species accumulate different acyl‐galactose components in response to the same stress. Additionally, the composition of the acyl‐galactose component of Arabidopsis acMGDG (galactose‐acylated monogalactosyldiacylglycerol) depends on the stress treatment. After sub‐lethal freezing treatment, acMGDG contained mainly non‐oxidized fatty acids esterified to galactose, whereas mostly oxidized fatty acids accumulated on galactose after wounding or bacterial infection. Compositional data are consistent with acMGDG being formed in vivo by transacylation with fatty acids from digalactosyldiacylglycerols. Oxophytodienoic acid, an oxidized fatty acid, was more concentrated on the galactosyl ring of acylated monogalactosyldiacylglycerols than in galactolipids in general. Also, oxidized fatty acid‐containing acylated monogalactosyldiacylglycerols increased cumulatively when wounded Arabidopsis leaves were wounded again. These findings suggest that, in Arabidopsis, the pool of galactose‐acylated monogalactosyldiacylglycerols may serve to sequester oxidized fatty acids during stress responses. 相似文献
55.
56.
57.
Bolen AL Naren AP Yarlagadda S Beranova-Giorgianni S Chen L Norman D Baker DL Rowland MM Best MD Sano T Tsukahara T Liliom K Igarashi Y Tigyi G 《Journal of lipid research》2011,52(5):958-970
Platelet activation initiates an upsurge in polyunsaturated (18:2 and 20:4) lysophosphatidic acid (LPA) production. The biochemical pathway(s) responsible for LPA production during blood clotting are not yet fully understood. Here we describe the purification of a phospholipase A(1) (PLA(1)) from thrombin-activated human platelets using sequential chromatographic steps followed by fluorophosphonate (FP)-biotin affinity labeling and proteomics characterization that identified acyl-protein thioesterase 1 (APT1), also known as lysophospholipase A-I (LYPLA-I; accession code O75608) as a novel PLA(1). Addition of this recombinant PLA(1) significantly increased the production of sn-2-esterified polyunsaturated LPCs and the corresponding LPAs in plasma. We examined the regioisomeric preference of lysophospholipase D/autotaxin (ATX), which is the subsequent step in LPA production. To prevent acyl migration, ether-linked regioisomers of oleyl-sn-glycero-3-phosphocholine (lyso-PAF) were synthesized. ATX preferred the sn-1 to the sn-2 regioisomer of lyso-PAF. We propose the following LPA production pathway in blood: 1) Activated platelets release PLA(1); 2) PLA(1) generates a pool of sn-2 lysophospholipids; 3) These newly generated sn-2 lysophospholipids undergo acyl migration to yield sn-1 lysophospholipids, which are the preferred substrates of ATX; and 4) ATX cleaves the sn-1 lysophospholipids to generate sn-1 LPA species containing predominantly 18:2 and 20:4 fatty acids. 相似文献
58.
Caloric restriction is a potent experimental manipulation that extends mean and maximum life span and delays the onset and progression of tumors in laboratory rodents. While caloric restriction (CR) clearly protects the genome from deleterious damage, the mechanism by which genomic stability is achieved remains unclear. We provide evidence that CR promotes genomic stability by increasing DNA repair capacity, specifically base excision repair (BER). CR completely reverses the age-related decline in BER capacity (P<0.01) in all tissues tested (brain, liver, spleen and testes) providing aged, CR animals with the BER phenotype of young, ad libitum-fed animals. This CR-induced reversal of the aged BER phenotype is accompanied by a reversal in the age-related decline in DNA polymerase beta (beta-pol), a rate-limiting enzyme in the BER pathway. CR significantly reversed the age-related loss of beta-pol protein levels (P<0.01), mRNA levels (P<0.01) and enzyme activity (P<0.01) in all tissues tested. Additionally, in young (4-6-month-old) CR animals a significant up-regulation in BER capacity, beta-pol protein and beta-pol mRNA is observed (P<0.01), demonstrating an early effect of CR that may provide insight in distinguishing the anti-tumor from the anti-aging effects of CR. This up-regulation in BER by caloric restriction in young animals corresponds to increased protection from carcinogen exposure, as mutation frequency is significantly reduced in CR animals exposed to either DMS or 2-nitropropane (2-NP) (P<0.01). Overall the data suggest an important biological consequence of moderate BER up-regulation and provides support for the hormesis theory of caloric restriction. 相似文献
59.
A. Venkateshwari K. Srimanjari A. Srilekha Ashrafunnisa Begum M. Sujatha T. Sunitha Pratibha Nallari A. Jyothy 《Indian journal of human genetics》2012,18(2):246-249
BACKGROUND:
Turner''s syndrome is the most common chromosomal abnormality in females, affecting 1 in 2,500 live female births. It is a result of absence of an X chromosome or the presence of a structurally abnormal X chromosome. Its most consistent clinical features are short stature and ovarian failure.AIM:
The aim of the study was to report a rare case of mosaic triple X syndrome in a female with primary amenorrhea.MATERIALS AND METHODS:
The chromosomal analysis using GTG banding was carried out, which revealed a mosaicism with 45,XO/47,XXX chromosomal constitution. Fluorescent in situ hybridization was also carried out to further confirm the observation made in the study.CONCLUSION:
The physical features presented by the female could be due to the 45,XO/47,XXX mosaicism and the karyotype analysis was consistent with the diagnosis and clinical symptoms. Triple X mosaicism was confirmed with conventional and molecular cytogenetic analysis. 相似文献60.
Jitendra A. Sattigeri Sachin Sethi Joseph A. Davis Shahadat Ahmed Geeta V. Rayasam Balasaheb G. Jadhav Satya M. Chilla Dhrubajyoti Datta A. Gadhave Vamshi K. Tulasi Tarun Jain Sreedhara Voleti Biju Benjamin Sunitha Udupa Garima Jain Yogender Singh Kona Srinivas Vinay S. Bansal Ian A. Cliffe 《Bioorganic & medicinal chemistry letters》2017,27(11):2313-2318
Designing drug candidates exhibiting polypharmacology is one of the strategies adopted by medicinal chemists to address multifactorial diseases. Metabolic disease is one such multifactorial disorder characterized by hyperglycaemia, hypertension and dyslipidaemia among others. In this paper we report a new class of molecular framework combining the pharmacophoric features of DPP4 inhibitors with those of ACE inhibitors to afford potent dual inhibitors of DPP4 and ACE. 相似文献