全文获取类型
收费全文 | 199篇 |
免费 | 9篇 |
国内免费 | 7篇 |
出版年
2022年 | 6篇 |
2021年 | 7篇 |
2020年 | 3篇 |
2019年 | 4篇 |
2018年 | 6篇 |
2017年 | 2篇 |
2016年 | 9篇 |
2015年 | 14篇 |
2014年 | 11篇 |
2013年 | 21篇 |
2012年 | 17篇 |
2011年 | 22篇 |
2010年 | 14篇 |
2009年 | 2篇 |
2008年 | 9篇 |
2007年 | 7篇 |
2006年 | 13篇 |
2005年 | 4篇 |
2004年 | 12篇 |
2003年 | 13篇 |
2002年 | 4篇 |
2001年 | 3篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 1篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1985年 | 1篇 |
1979年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有215条查询结果,搜索用时 15 毫秒
11.
Joseph Y. Kim Arumugam Balamurugan Kodi Azari Christian Hofmann Hwee L. Ng Elaine F. Reed Suzanne McDiarmid Otto O. Yang 《PloS one》2015,10(8)
Immune prophylaxis and treatment of transplanted tissue rejection act indiscriminately, risking serious infections and malignancies. Although animal data suggest that cellular immune responses causing rejection may be rather narrow and predictable based on genetic background, there are only limited data regarding the clonal breadth of anti-donor responses in humans after allogeneic organ transplantation. We evaluated the graft-infiltrating CD8+ T lymphocytes in skin punch biopsies of a transplanted hand over 178 days. Profiling of T cell receptor (TCR) variable gene usage and size distribution of the infiltrating cells revealed marked skewing of the TCR repertoire indicating oligoclonality, but relatively normal distributions in the blood. Although sampling limitation prevented complete assessment of the TCR repertoire, sequencing further identified 11 TCR clonal expansions that persisted through varying degrees of clinical rejection and immunosuppressive therapy. These 11 clones were limited to three TCR beta chain variable (BV) gene families. Overall, these data indicate significant oligoclonality and likely restricted BV gene usage of alloreactive CD8+ T lymphocytes, and suggest that changes in rejection status are more due to varying regulation of their activity or number rather than shifts in the clonal populations in the transplanted organ. Given that controlled animal models produce predictable BV usage in T lymphocytes mediating rejection, understanding the determinants of TCR gene usage associated with rejection in humans may have application in specifically targeted immunotherapy. 相似文献
12.
13.
Yao X Balamurugan P Arvey A Leslie C Zhang L 《Biochemical and biophysical research communications》2010,403(1):30-35
Protein tyrosine kinases play key roles in many molecular and cellular processes in diverse living organisms. Their proper functioning is crucial for the normal growth, development, and health in humans, whereas their dysfunction can cause serious diseases, including various cancers. As such, intense studies have been performed to understand the molecular mechanisms by which the activities of protein tyrosine kinases are regulated in mammalian cells. Particularly, small molecules that can modulate the activity of tyrosine kinases are of great importance for discovering therapeutic drug candidates for numerous diseases. Notably, heme cannot only serve as a prosthetic group for hemoglobins and enzymes, but it also is a small signaling molecule that can control the activity of diverse signaling and regulatory proteins. Using a computational search, we found that a group of non-membrane spanning tyrosine kinases contains one or more CP motifs that can potentially bind to heme and mediate heme regulation. We then used experimental approaches to determine whether heme can affect the activity of any of these tyrosine kinases. We found that heme indeed affects the phosphorylation of key tyrosine residues in Jak2 and Src, and is therefore able to modulate Jak2 and Src activity. Further experiments showed that Jak2 and Src bind to heme and that the presence of heme alters the sensitivity of Jak2 and Src to trypsin digestion. These results suggest that heme actively interacts with Jak2 and Src and alters their conformation. 相似文献
14.
Thirumangalathu R Krishnan S Bondarenko P Speed-Ricci M Randolph TW Carpenter JF Brems DN 《Biochemistry》2007,46(21):6213-6224
Oxidation of methionine residues is involved in several biochemical processes and in degradation of therapeutic proteins. The relationship between conformational stability and methionine oxidation in recombinant human interleukin-1 receptor antagonist (rhIL-1ra) was investigated to document how thermodynamics of unfolding affect methionine oxidation in proteins. Conformational stability of rhIL-1ra was monitored by equilibrium urea denaturation, and thermodynamic parameters of unfolding (DeltaGH2O, m, and Cm) were estimated at different temperatures. Methionine oxidation induced by hydrogen peroxide at varying temperatures was monitored during "coincubation" of rhIL-1ra with peptides mimicking specific regions of the reactive methionine residues in the protein. The coincubation study allowed estimation of oxidation rates in protein and peptide at each temperature from which normalized oxidation rate constants and activation energies were calculated. The rate constants for buried Met-11 in the protein were lower than for methionine in the peptide with an associated increase in activation energy. The rate constants and activation energy of solvent exposed methionines in protein and peptide were similar. The results showed that conformational stability, monitored using the Cm value, has an effect on oxidation rates of buried methionines. The rate constant of buried Met-11 correlated well with the Cm value but not DeltaGH2O. No correlation was observed for the oxidation rates of solvent-exposed methionines with any thermodynamic parameters of unfolding. The findings presented have implications in protein engineering, in design of accelerated stability studies for protein formulation development, and in understanding disease conditions involving protein oxidation. 相似文献
15.
16.
Culture and molecular-based techniques were used to characterize bacterial diversity in the cooling water system of a fast breeder test reactor (FBTR). Techniques were selected for special emphasis on sulphate-reducing bacteria (SRB). Water samples from different locations of the FBTR cooling water system, in addition to biofilm scrapings from carbon steel coupons and a control SRB sample were characterized. Whole genome extraction of the water samples and SRB diversity by group specific primers were analysed using nested PCR and denaturing gradient gel electrophoresis (DGGE). The results of the bacterial assay in the cooling water showed that the total culturable bacteria (TCB) ranged from 10(3) to 10(5)?cfu?ml(-1); iron-reducing bacteria, 10(3) to 10(5)?cfu?ml(-1); iron oxidizing bacteria, 10(2) to 10(3)?cfu?ml(-1) and SRB, 2-29?cfu?ml(-1). However, the counts of the various bacterial types in the biofilm sample were 2-3 orders of magnitude higher. SRB diversity by the nested PCR-DGGE approach showed the presence of groups 1, 5 and 6 in the FBTR cooling water system; however, groups 2, 3 and 4 were not detected. The study demonstrated that the PCR protocol influenced the results of the diversity analysis. The paper further discusses the microbiota of the cooling water system and its relevance in biofouling. 相似文献
17.
R. Sindhu P. Govindaraj A. Balamurugan C. Appunu 《Journal of plant biochemistry and biotechnology.》2011,20(1):118-124
Understanding the pattern of diversity among the commercial sugarcane hybrids is highly useful to sugarcane breeders in planning and broadening the genetic base. Genetic analysis of 22 cultivated sugarcane hybrids representing all agro-eco climatic regions of tropical India was carried out using ten sequence tagged microsatellite sites (STMS) primers. A total of 127 markers were amplified, of which 78.74% were polymorphic with an average of 10 polymorphic products per STMS primer. Jaccard’s similarity coefficient value estimated between closely related hybrids was 0.889 while the lowest coefficient value of 0.574 was detected with distantly related hybrids. The average genetic similarity among the hybrids was ~84.8%. These results indicated the existence of low level of genetic diversity among the commercial hybrids under cultivation. Unweighted pair group method with arithmetic averages (UPGMA) cluster analysis detected five major clusters. Cluster II consisted of four varieties which had Co 775 as one of the parents. Variety CoC 671 and its somaclone Co 94012 were grouped into cluster IIa. Varieties grouped in the cluster III had either CoC 671 or Co 775 in their genealogy indicating the influence of parental genome contribution to clustering. Varieties developed for east coast zone were grouped in the clusters IIb, IIIb, IIIc and IVe which indicated the influence of adaptation of varieties to particular agro-climatic condition. The study also identified 12 unique markers which can be useful in varietal identification and rouging in seed plot. 相似文献
18.
R.?A.?NazeerEmail author R.?Deeptha R.?Jaiganesh N.?S.?Sampathkumar Shabeena?Yousuf?Naqash 《International journal of peptide research and therapeutics》2011,17(3):209-216
We have investigated the antioxidant activity of protein hydrolysates prepared from backbones of two commercially important
fishes; seela (Sphyraena barracuda) and ribbon fish (Lepturacanthus savala). Pepsin and trypsin hydrolysates were found more potent to inhibit lipid peroxidation in case of ribbon and seela fish respectively
and were further purified by using fast protein liquid chromatography on anion exchange and gel filtration chromatography.
The active peaks after gel filtration chromatography of seela fish was able to scavenge 2,2-diphenyl-1-picryhydrazyl and hydroxyl
radicals by 61 ± 2.3 and 58.7 ± 2.3% and ribbon fish hydrolysate by 60.0 ± 2.6 and 55.6 ± 1.8% as measured by ESR spectroscopy.
And the active fractions showed presence of both essential and non-essential amino acids with high percentages of arginine
(11.95 and 12.76%) and lysine (13.49 and 13.89%). 相似文献
19.
Thachamvally Riyesh Vinayagamurthy Balamurugan Arnab Sen Veerakyathappa Bhanuprakash Gnanavel Venkatesan Vinita Yadav Raj Kumar Singh 《中国病毒学》2011,26(5):324-337
In this study, thermo-adapted (Ta) PPR vaccines were assessed for their stability at 25, 37, 40, 42 and 45°C in lyophilized
form using two extrinsic stabilizers {lactalbumin hydrolysate-sucrose (LS) and stabilizer E} and in reconstituted form with
the diluents (1 mol/L MgSO4 or 0.85% NaCl). The lyophilized vaccines showed an expiry period of 24–26 days at 25°C, 7–8 days at 37°C and 3–4 days at
40°C. LS stabilizer was superior at 42°C with a shelf-life of 44 h, whereas in stabilizer E, a 40 h shelf-life with a comparable
half-life was observed. At 45°C, the half-life in stabilizer E was better than LS and lasted for 1 day. Furthermore, the reconstituted
vaccine maintained the titre for 48 h both at 4°C and 25°C and for 24–30 h at 37°C. As both the stabilizers performed equally
well with regard to shelf-life and half-life, the present study suggests LS as stabilizer as a choice for lyophilization with
0.85% NaCl diluent, because it has better performance at higher temperature. These Ta vaccines can be used as alternatives
to existing vaccines for the control of the disease in tropical countries as they are effective in avoiding vaccination failure
due to the breakdown in cold-chain maintenance, as this vaccine is considerably more stable at ambient temperatures. 相似文献
20.
Jagadeesan B Fleishman Littlejohn AE Amalaradjou MA Singh AK Mishra KK La D Kihara D Bhunia AK 《PloS one》2011,6(6):e20694