全文获取类型
收费全文 | 882篇 |
免费 | 76篇 |
出版年
2022年 | 8篇 |
2021年 | 20篇 |
2020年 | 13篇 |
2019年 | 18篇 |
2018年 | 27篇 |
2017年 | 11篇 |
2016年 | 27篇 |
2015年 | 40篇 |
2014年 | 58篇 |
2013年 | 57篇 |
2012年 | 68篇 |
2011年 | 59篇 |
2010年 | 45篇 |
2009年 | 39篇 |
2008年 | 50篇 |
2007年 | 40篇 |
2006年 | 30篇 |
2005年 | 28篇 |
2004年 | 24篇 |
2003年 | 24篇 |
2002年 | 25篇 |
2001年 | 9篇 |
2000年 | 25篇 |
1999年 | 10篇 |
1998年 | 7篇 |
1997年 | 4篇 |
1996年 | 7篇 |
1995年 | 9篇 |
1993年 | 5篇 |
1992年 | 11篇 |
1991年 | 5篇 |
1990年 | 9篇 |
1989年 | 8篇 |
1988年 | 8篇 |
1987年 | 5篇 |
1986年 | 5篇 |
1985年 | 5篇 |
1984年 | 11篇 |
1983年 | 7篇 |
1982年 | 8篇 |
1981年 | 4篇 |
1979年 | 13篇 |
1978年 | 9篇 |
1977年 | 7篇 |
1975年 | 9篇 |
1974年 | 7篇 |
1973年 | 4篇 |
1972年 | 5篇 |
1971年 | 4篇 |
1970年 | 6篇 |
排序方式: 共有958条查询结果,搜索用时 367 毫秒
1.
M. Gopalakrishnan P. Sureshkumar J. Thanusu V. Kanagarajan 《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):347-351
Compound 26 is more potent against Escherichia coli. and 24 is more active against Staphylococcus aureus, β-Heamolytic streptococcus, Vibreo cholerae, Salmonella typhii, and Shigella flexneri than the standard drug ciprofloxacin. Moreover, of all the compounds tested, 26 is more effective against Aspergillus flavus and Mucor, than the standard drug fluconazole. 相似文献
2.
3.
Carcinogen-nucleic acid interactions: equilibrium binding studies of aflatoxins B1 and B2 with DNA and the oligodeoxynucleotide d(ATGCAT)2 总被引:3,自引:0,他引:3
M P Stone S Gopalakrishnan T M Harris D E Graves 《Journal of biomolecular structure & dynamics》1988,5(5):1025-1041
Equilibrium binding is believed to play an important role in directing the subsequent covalent attachment of many carcinogens to DNA. We have utilized UV spectroscopy to examine the non-covalent interactions of aflatoxin B1 and B2 with calf thymus DNA, poly(dAdT):poly(dAdT), and poly(dGdC):poly(dGdC), and have utilized NMR spectroscopy to examine non-covalent interactions of aflatoxin B2 with the oligodeoxynucleotide d(ATGCAT)2. UV-VIS binding isotherms suggest a greater binding affinity for calf thymus DNA and poly(dAdT):poly(dAdT) than for poly(dGdC):poly(dGdC). Scatchard analysis of aflatoxin B1 binding to calf thymus DNA in 0.1 M NaCl buffer indicates that binding of the carcinogen at levels of bound aflatoxin less than 1 carcinogen per 200 base pairs occurs with positive cooperativity. The cooperative binding effect is dependent on the ionic strength of the medium; when the NaCl concentration is reduced to 0.01 M, positive cooperativity is observed at carcinogen levels less than 1 carcinogen per 500 base pairs. The Scatchard data may be fit using a "two-site" binding model [L.S. Rosenberg, M.J. Carvlin, and T.R. Krugh, Biochemistry 25, 1002-1008 (1986)]. This model assumes two independent sets of binding sites on the DNA lattice, one a high affinity site which binds the carcinogen with positive cooperativity, the second consisting of lower affinity binding sites to which non-specific binding occurs. NMR analysis of aflatoxin B2 binding to d(ATGCAT)2 indicates that the aflatoxin B2/oligodeoxynucleotide complex is in fast exchange on the NMR time scale. Upfield chemical shifts of 0.1-0.5 ppm are observed for the aflatoxin B2 4-OCH3, H5, and H6a protons. Much smaller chemical shift changes (less than or equal to 0.06 ppm) are observed for the oligodeoxynucleotide protons. The greatest effect for the oligodeoxynucleotide protons is observed for the adenine H2 protons, located in the minor groove. Nonselective T1 experiments demonstrate a 15-25% decrease in the relaxation time for the adenine H2 protons when aflatoxin B2 is added to the solution. This result suggests that aflatoxin B2 protons in the bound state may be in close proximity to these protons, providing a source of dipolar relaxation. Further experiments are in progress to probe the nature of the aflatoxin B1 and B2 complexes with polymeric DNA and oligodeoxynucleotides, and to establish the relationship between the non-covalent DNA-carcinogen complexes observed in these experiments, and covalent aflatoxin B1-guanine N7 DNA adducts. 相似文献
4.
Bhuvana Gopalakrishnan Burachai Sonthayanon Rownak Rahmatullah Subbaratnam Muthukrishnan 《Plant molecular biology》1991,16(3):463-467
Protoplasts were prepared from barley aleurone layers using Onozuka cellulase digestion and purification through a Percoll gradient. Protoplasts prepared by this procedure had a viability ranging from 60% to 80% during the first two days of culture. They were responsive to gibberellic acid (GA) as measured by the stimulation of -amylase synthesis. The GA stimulation was counteracted by abscisic acid (ABA). In the presence of polyethylene glycol (PEG), the protoplasts took up exogenously added plasmid DNA containing the reporter gene coding for chloramphenicol acetyl transferase (CAT) linked to a 35S promoter from cauliflower mosaic virus (CaMV) or to barley -amylase gene promoters and expressed CAT activity. Therefore, barley aleurone layer protoplasts are suitable for analysis of hormoneresponsive elements in hydrolase genes. 相似文献
5.
Carbonic anhydrase II deficiency: diagnosis and carrier detection using differential enzyme inhibition and inactivation. 总被引:12,自引:1,他引:11 下载免费PDF全文
V Sundaram P Rumbolo J Grubb P Strisciuglio W S Sly 《American journal of human genetics》1986,38(2):125-136
Carbonic anhydrase (CA) I and II are soluble isozymes that represent the major nonhemoglobin proteins in the erythrocyte. We recently identified a deficiency of CA II as the enzymatic basis for the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. Virtual absence of the CA II peak on high-performance liquid chromatography, of CA II esterase activity, and of immunoprecipitable CA II were demonstrated on extracts of red cell lysates from all patients studied. Reduced levels of CA II were found in obligate heterozygotes. Here, we present evidence that CA II in red cell lysates can be quantitated by measuring CO2 hydratase activity in the presence of inhibitors that selectively inhibit the activity of CA I to a much greater extent than that of CA II. This was done with iodide (anion binding) and bromopyruvic acid (alkylation), and the respective assays evaluated as diagnostic tools for CA II deficiency in human red cells. These techniques greatly simplify the quantitation of CA II in hemolysates and should make genetic diagnosis and counseling for the newly described inborn error of metabolism due to CA II deficiency generally available. They also allow quantitation of CA I in red cell lysates. 相似文献
6.
7.
Antibodies were elicited in rabbits to the dinucleotide, dpTpA, conjugated to a carrier protein. Among a few deoxyribomono- and oligonucleotides tested for binding to the antibodies by nitrocellulose tilter binding assay, only dpTpA and dpTpA containing oligonucleotides showed binding. The inhibition of the binding of 3H-dpTpA to the antibodies by various nonradioactive mono- and oligonucleotides showed that the antibodies were sequence specific and recognized the whole molecule of dpTpA. dpTpA specific antibodies were purified by a two step affinity chromatography. By competition studies, it was found that the purified antibodies bound denatured DNA at dpTpA sequences. The antibodies did not bind RNA. 相似文献
8.
Clonidine, when administered for prolonged period showed no tolerance to its analgesic activity. Prior exposure to clonidine attenuated the tolerance development to morphine-induced analgesia and the supersensitivity to acetylcholine (ACh) in ileum during chronic morphine treatment. Further, acute administration of lower doses of clonidine (upto 1 mg) produced supersensitivity in ileum to ACh while the higher dose (10 mg) induced subsensitivity. In vas deferens, clonidine in all the concentrations tested induced dose and time dependent supersensitivity to norepinephrine (NE) similar to that produced by morphine. Chronic clonidine treatment failed to alter the ACh responses in ileum while it produced supersensitivity to NE in vas deferens. The results suggest that clonidine and morphine possess comparable properties and the antagonism of chronic morphine tolerance by clonidine may be the therapeutic basis for its clinical application in the treatment of opiate addicts. 相似文献
9.
Nature of the Complementation Products Formed by a Complementing Mutant of Neurospora crassa 总被引:1,自引:0,他引:1 下载免费PDF全文
The mutant am-14 produces no active nicotinamide adenine dinucleotide phosphate-linked glutamate dehydrogenase (GDH) and no protein showing immunological cross-reaction with the enzyme. Nevertheless, it shows complementation with several other am mutants in heterokaryons. Active GDH can be extracted from heterokaryons formed from am-14 and other mutants which, by themselves, produce more or less inactive varieties of the enzyme. The enzyme from am-14 + am-3 heterokaryons can be partially separated from am-3 mutant GDH on a diethylaminoethyl cellulose column. It is characterized by abnormally high thermolability and by a capacity for activation by glutamate. By the same procedure as brings about hybridization between mutant GDH proteins, it has been possible to recover enzyme with the properties of pure am-3 GDH from a partially purified am-14 + am-3 GDH preparation which was initially substantially free of unhybridized am-3 enzyme. This is interpreted as evidence that the active complementation product is a hybrid oligomer containing am-3 monomers and also am-14 monomers, the latter being unable to aggregate by themselves. Heterokaryons formed from am-14 and wild type produce GDH of abnormally high thermolability, presumably due to the formation of am-14 + am(+) hybrids. 相似文献
10.
Gopalakrishnan S Boyle D Takemoto L 《Transactions of the Kansas Academy of Science. Kansas Academy of Science》1993,96(1-2):7-12
The alpha crystallins are cytosolic proteins that co-localize and co-purify with actin-containing microfilaments. Affinity column chromatography employing both covalently-coupled actin or alpha crystallin was used to demonstrate specific and saturable binding of actin with alpha crystallin. This conclusion was confirmed by direct visualization of alpha aggregates bound to actin polymerized in vitro. The significance of this interaction in relation to the functional properties of these two polypeptides will be discussed. 相似文献