全文获取类型
收费全文 | 345篇 |
免费 | 30篇 |
出版年
2023年 | 3篇 |
2022年 | 6篇 |
2021年 | 20篇 |
2020年 | 14篇 |
2019年 | 3篇 |
2018年 | 10篇 |
2017年 | 8篇 |
2016年 | 12篇 |
2015年 | 12篇 |
2014年 | 11篇 |
2013年 | 29篇 |
2012年 | 15篇 |
2011年 | 19篇 |
2010年 | 10篇 |
2009年 | 19篇 |
2008年 | 17篇 |
2007年 | 20篇 |
2006年 | 14篇 |
2005年 | 16篇 |
2004年 | 16篇 |
2003年 | 9篇 |
2002年 | 12篇 |
2001年 | 6篇 |
2000年 | 7篇 |
1999年 | 2篇 |
1998年 | 2篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1993年 | 3篇 |
1992年 | 4篇 |
1991年 | 4篇 |
1990年 | 8篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1986年 | 5篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 5篇 |
1981年 | 1篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1974年 | 1篇 |
1973年 | 3篇 |
1972年 | 2篇 |
排序方式: 共有375条查询结果,搜索用时 156 毫秒
81.
Casteleijn MG Alahuhta M Groebel K El-Sayed I Augustyns K Lambeir AM Neubauer P Wierenga RK 《Biochemistry》2006,45(51):15483-15494
The importance of the fully conserved active site proline, Pro168, for the reaction mechanism of triosephosphate isomerase (TIM) has been investigated by studying the enzymatic and crystallographic properties of the P168A variant of trypanosomal TIM. In TIM, Pro168 follows the key catalytic residue Glu167, situated at the beginning of the flexible active site loop (loop 6). Turnover numbers of the P168A variant for its substrates are reduced approximately 50-fold, whereas the Km values are approximately 2 times lower. The affinity of the P168A variant for the transition state analogue 2-phosphoglycolate (2PG) is reduced 5-fold. The crystal structures of unliganded and liganded (2PG) P168A show that the phosphate moiety of 2PG is bound similarly as in wild-type TIM, whereas the interactions of the carboxylic acid moiety with the side chain of the catalytic Glu167 differ. The unique properties of the proline side chain at position 168 are required to transmit ligand binding to the conformational change of Glu167: the side chain of Glu167 flips from the inactive swung-out to the active swung-in conformation on ligand binding in wild-type TIM, whereas in the mutant this conformational change does not occur. Further structural comparisons show that in the wild-type enzyme the concerted movement of loop 6 and loop 7 from unliganded-open to liganded-closed appears to be facilitated by the interactions of the phosphate moiety with loop 7. Apparently, the rotation of 90 degrees of the Gly211-Gly212 peptide plane of loop 7 plays a key role in this concerted movement. 相似文献
82.
83.
F. F. Abdel-Motaal M. S. M. Nassar S. A. El-Zayat M. A. El-Sayed S. Ito 《Folia microbiologica》2009,54(3):207-212
Antifungal activity of hyoscyamine (Hcy) and scopolamine (Sco) were determined by TLC-bioautography against fungi associated
with H. muticus grown in Egypt, and those isolated from other plants grown in Japan. All 40 fungal strains were tolerant to Sco and sensitive
to Hcy, exhibiting a growth inhibition zone around the Hcy spot on the bioautography plate. The strains were grouped into
three types based on the appearance of the inhibition zone: (i) 17 strains exhibiting a clear inhibition zone, which remained clear at 8 d after incubation (type I); (ii) 22 strains exhibiting the inhibition zone with a brown circle surrounding the zone and regrowth within the inhibition zone
(type II); (iii) 1 strain exhibiting the inhibition zone with no brown circle and regrowth within the inhibition zone (type III). In the type II and III strains, Hcy disappeared, and other alkaloids were found in the inhibition zones in its place. Hcy feeding experiments using
Penicillium purpurogenum (type II) and Cunninghamella elegans (type III) revealed that these fungi may convert Hcy to a new alkaloid compound. 相似文献
84.
Ashraf S. A. El-Sayed 《Indian journal of microbiology》2009,49(3):243-250
Solid state fermentation was conducted for the production of L-glutaminase by Trichoderma koningii Oud.aggr. using different agro-industrial byproducts inlcuding wheat bran, groundnut residues, rice hulls, soya bean meal,
corn steep, sesamum oil cake, cotton seed residues and lentil industrial residues as solid substrates. Wheat bran was the
best substrate for induction of L-glutaminase (12.1 U/mg protein) by T. koningii. The maximum productivity (23.2 U/mg protein) and yield (45.0 U/gds) of L-glutaminase by T. koningii occurred using wheat bran of 70% initial moisture content, initial pH 7.0, supplemented with D-glucose (1.0%) and L-glutamine
(2.0% w/v), inoculated with 3 ml of 6 day old fungal culture and incubated at 30°C for 7 days. After optimization, the productivity
of L-glutaminase by the solid cultures of T. koningii was increased by 2.2 fold regarding to the submerged culture. 相似文献
85.
Highly concentrated aqueous solutions of acrylamide (Am) were polymerized in presence of polyethylene glycol (PEG) using ammonium persulfate as initiator under different conditions including ammonium persulfate concentration (0.02–0.06 g/gAm) temperature (60–95 °C), Am/PEG400 ratio (1/1–1/5 g/g), PEG molecular weight (400–6000). At optimum reaction conditions a PEG 400/PAm adduct was prepared with a % total conversion of 99.7 in 2 min using ammonium persulfate (0.05 g/gAm), Am/PEG (1/2 g/g) at 70 °C. The structure of the adduct was confirmed by FT-IR spectra. The adduct was utilized as a finishing additive for cotton fabric in presence and absence of dimethyloldihydroxy ethylene urea (DMDHEU) by the bad – dry – cure method. In absence of DMDHEU, the adduct improves the fabric tensile strength, stiffness and oily stain release rating without affect the wettability along with decreasing the fabric resiliency compared to the blank sample. Inclusion DMDHEU the finishing bath (50 g/l) results in improving the fabric resiliency and stiffness as well as decreasing the strength, wettability and oily stain release compared to those of fabric treated with adduct in absence of DMDHEU. However, at an adduct concentration of 40 g/l and in presence of 50 g/l DMDHEU the fabric properties are in general, superior to those of blank fabric. 相似文献
86.
Mohammad Raish Varinderpal S Dhillon Arif Ahmad Mushtaq Ahmad Ansari Shahid Mudassar Mohammad Shahid Vineeta Batra Pawan Gupta Bhudev Chandra Das NK Shukla Syed Akhtar Husain 《Translational oncology》2009,2(4):264-270
BACKGROUND: Aberrant DNA methylation has been recognized in human breast carcinogenesis as a common molecular alteration associated with the loss of expression of a number of key regulatory genes. The present study was undertaken to determine whether methylation and expression of p16 and FHIT genes would correlate with the estrogen receptor (ER) and progesterone receptor (PR) status. METHODS: Methylation-specific polymerase chain reaction, messenger RNA (mRNA) expression analysis, immunohistochemistry, and Western blot analysis were performed to study the methylation of p16 and FHIT genes in 351 pairs of malignant/normal breast tissues. We examined the expression of ER and PR in those specimens by immunohistochemistry. Mutations of p16 and FHIT genes in tumors were detected by direct sequencing. RESULTS: The frequency of hypermethylation was 31.9% and 36.8% in p16 and FHIT genes, respectively, and showed significant harmony in concordant hypermethylation (P < .0001). In postmenopausal patients, methylation frequency in both genes is significantly higher in poorly and moderately differentiated tumors. Loss of protein expression of p16 and FHIT in 77 and 74 tumors, respectively, is associated with their methylation status in premenopausal women. CONCLUSION: We did not find any significant differences in tumor-related gene methylation patterns relevant to both ER and PR status of breast tumors. 相似文献
87.
Fatmah A.M. Al-Omary Laila A. Abou-zeid Mahmoud N. Nagi El-Sayed E. Habib Alaa A.-M. Abdel-Aziz Adel S. El-Azab Sami G. Abdel-Hamide Mohamed A. Al-Omar Abdulrahman M. Al-Obaid Hussein I. El-Subbagh 《Bioorganic & medicinal chemistry》2010,18(8):2849-2863
A new series of 2,6-substituted-quinazolin-4-ones was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 22, 33–37, 39–43, and 45 proved to be active DHFR inhibitors with IC50 range of 0.4–1.0 μM. Compound 18 showed broad-spectrum antimicrobial activity comparable to the known antibiotic gentamicin. Compounds 34 and 36 showed antitumor activity at GI50 (MG-MID) concentrations of 11.2, and 24.2 μM, respectively. Molecular modeling study including flexible alignment; electrostatic, hydrophobic mappings; and pharmacophore prediction were performed. A main featured pharmacophore model was developed which justifies the importance of the main pharmacophoric groups as well as of their relative distances. The substitution pattern and spatial considerations of the π-systems in regard to the quinazoline nucleus proved critical for biological activity. 相似文献
88.
Amal A. Sallam Yukio Hitotsuyanagi El-Sayed S. Mansour Atallah F. Ahmed Sahar Gedara Haruhiko Fukaya Koichi Takeya 《Phytochemistry letters》2010,3(3):117-121
From the roots of Bryonia cretica L. two new cucurbitacins, isocucurbitacins G (1) and H (2), along with three known cucrbitacins, cucurbitacins G (3), H (4), and J (5) were isolated. The structures of 1 and 2 were determined on the basis of 1D and 2D NMR spectroscopic analysis and X-ray crystallography. The relative stereochemistries of the side chains of 3–5 were also established by comparison of their NMR data and X-ray crystallography. 相似文献
89.
Temperature jump-induced secondary structural change of the membrane protein bacteriorhodopsin in the premelting temperature region: a nanosecond time-resolved Fourier transform infrared study 下载免费PDF全文
The secondary structural changes of the membrane protein, bacteriorhodopsin, are studied during the premelting reversible transition by using laser-induced temperature jump technique and nanosecond time-resolved Fourier transform infrared spectroscopy. The helical structural changes are triggered by using a 15 degrees C temperature jump induced from a preheated bacteriorhodopsin in D2O solution at a temperature of 72 degrees C. The structural transition from alphaII- to alphaI-helices is observed by following the change in the frequency of the amide I band from 1667 to 1651 cm-1 and the shift in the frequency of the amide II vibration from 1542 cm-1 to 1436 cm-1 upon H/D exchange. It is found that although the amide I band changes its frequency on a time scale of <100 ns, the H/D exchange shifts the frequency of the amide II band and causes a complex changes in the 1651-1600 cm-1 and 1530-1430 cm-1 frequency region on a longer time scale (>300 ns). Our result suggests that in this "premelting transition" temperature region of bacteriorhodopsin, an intrahelical conformation conversion of the alphaII to alphaI leads to the exposure of the hydrophobic region of the protein to the aqueous medium. 相似文献
90.
The ability of Cu(II)(2)(3,5-diisopropylsalicylate)(4), CuDIPS, which exhibits superoxide dismutase (SOD)-like activity, to prevent cisplatin-induced nephrotoxicity was examined in rats. Rats were divided into four groups and treated as follows: (i) vehicle control; (ii) cisplatin (16 mg/kg, intraperitoneally); (iii) CuDIPS (10 mg/kg, intraperitoneally); and (iv) cisplatin plus CuDIPS. Rats were sacrificed 3 days post-treatment. Cisplatin alone resulted in significantly increased plasma creatinine and urea. Administration of 10 mg/kg CuDIPS prevented the cisplatin-induced elevation of plasma creatinine and urea and protected against kidney damage. Relative to controls, rats that received cisplatin treatment displayed a decrease of reduced glutathione (GSH) and elevated platinum and thiobarbituric acid reactive substances (TBARS) levels in the kidney. In comparison with controls, activities of antioxidant enzymes (SOD, CAT, GSH-Px and GSH-Rd) were also reduced in the kidney of rats treated with cisplatin. Administration of 10 mg/kg CuDIPS prevented cisplatin-induced alterations in renal platinum, GSH, TBARS, and antioxidant enzyme activities. This study suggests that the protection offered by CuDIPS against cisplatin-induced nephrotoxicity is partly related to maintenance of renal antioxidant systems. 相似文献