全文获取类型
收费全文 | 1124篇 |
免费 | 64篇 |
国内免费 | 1篇 |
出版年
2023年 | 6篇 |
2022年 | 13篇 |
2021年 | 23篇 |
2020年 | 15篇 |
2019年 | 10篇 |
2018年 | 24篇 |
2017年 | 18篇 |
2016年 | 22篇 |
2015年 | 41篇 |
2014年 | 58篇 |
2013年 | 84篇 |
2012年 | 80篇 |
2011年 | 67篇 |
2010年 | 42篇 |
2009年 | 37篇 |
2008年 | 60篇 |
2007年 | 60篇 |
2006年 | 57篇 |
2005年 | 54篇 |
2004年 | 44篇 |
2003年 | 41篇 |
2002年 | 34篇 |
2001年 | 21篇 |
2000年 | 21篇 |
1999年 | 13篇 |
1998年 | 15篇 |
1997年 | 8篇 |
1993年 | 5篇 |
1992年 | 13篇 |
1991年 | 7篇 |
1990年 | 10篇 |
1989年 | 9篇 |
1988年 | 10篇 |
1987年 | 10篇 |
1986年 | 10篇 |
1985年 | 13篇 |
1984年 | 6篇 |
1983年 | 9篇 |
1981年 | 7篇 |
1980年 | 6篇 |
1979年 | 7篇 |
1978年 | 7篇 |
1977年 | 8篇 |
1976年 | 5篇 |
1975年 | 7篇 |
1974年 | 11篇 |
1973年 | 14篇 |
1972年 | 10篇 |
1971年 | 5篇 |
1969年 | 7篇 |
排序方式: 共有1189条查询结果,搜索用时 15 毫秒
61.
Kapoor M Anand N Koul S Chimni SS Manhas KS Raina C Parshad R Taneja SC Qazi GN 《Bioorganic chemistry》2003,31(3):259-269
(R)- and (S)-1-chloro-3-(1-naphthyloxy)-2-propanol are intermediates in the synthesis of β-adrenergic blocking agents and antihypertensive drugs such as propranolol and nadoxolol. Herein, improvement in the preparation of racemic 1-chloro-3-(1-naphthyloxy)-2-propanol generated from 1-naphthol and epichlorohydrin are reported. In addition, kinetic resolution studies have been conducted to obtain both (R) and (S)-1-chloro-3-(1-naphthyloxy)-2-propanol. These compounds were obtained in highly optically pure form by the stereoselective hydrolysis of its acyl derivatives using whole cell preparations containing enzymes from native sources. The results were compared with those obtained using commercial lipases. 相似文献
62.
Phadke SM Islam K Deslouches B Kapoor SA Beer Stolz D Watkins SC Montelaro RC Pilewski JM Mietzner TA 《Peptides》2003,24(8):1099-1107
Lentivirus lytic peptides (LLPs) are derived from HIV-1 and have antibacterial properties. LLP derivatives (eLLPs) were engineered for greater potency against Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA). Minimum bactericidal concentration (MBC) was determined in low and physiologic salt concentrations. MBC was decreased against SA and equivalent against PA in physiologic salt when compared to the parent compound LLP1. In a novel cystic fibrosis (CF) airway cell model, one derivative, WLSA5, reduced the number of adherent PA and only moderately affected CF cell viability. Overall, eLLPs are selectively toxic to bacteria and may be useful against CF airway infections. 相似文献
63.
Piperazinyl-linked fluoroquinolone dimers possessing potent antibacterial activity against drug-resistant strains of Staphylococcus aureus 总被引:1,自引:0,他引:1
Kerns RJ Rybak MJ Kaatz GW Vaka F Cha R Grucz RG Diwadkar VU Ward TD 《Bioorganic & medicinal chemistry letters》2003,13(10):1745-1749
The synthesis of symmetric and asymmetric piperazinyl-linked dimers of the fluoroquinolone class of antibiotics is described. Specific dimers are shown to possess potent antibacterial activity against drug-resistant strains of Staphylococcus aureus, including strains possessing resistance due to the NorA multidrug efflux pump and a mutation in the quinolone resistance-determining region of topoisomerase IV. 相似文献
64.
Effect of amino acids on production of xylanase and pectinase from Streptomyces sp. QG-11-3 总被引:5,自引:0,他引:5
Qasim Khalil Beg Bharat Bhushan Mukesh Kapoor G.S. Hoondal 《World journal of microbiology & biotechnology》2000,16(2):211-213
Xylanase and pectinase production by Streptomyces sp. QG-11-3 was stimulated by DL-norleucine, L-leucine, DL-isoleucine, L-lysine monohydrochloride and DL--phenylalanine by up to 3.72- and 2.78-fold, respectively, whereas the combination of DL-norleucine, L-leucine and DL-isoleucine synergistically stimulated the xylanase and pectinase production by up to 6.72- and 5.62-fold, respectively. Glycine, DL-norvaline, DL-methionine, and DL-aspartic acid showed no significant stimulatory effect on enzyme production. 相似文献
65.
Kynurenine, a metabolite of tryptophan along the 'kynurenine pathway', is at a branch point of the pathway which can lead to the synthesis of both quinolinic acid (QUIN) and kynurenic acid (KYNA). KYNA is an antagonist of glutamate receptors; however, QUIN is a selective agonist of NMDA receptors, and has been shown to act as an excitotoxic agent. A high QUIN/KYNA ratio has been implicated in a variety of neurological diseases in which excitotoxic neuronal cell death is found, e.g. AIDS-related dementia, stroke, etc. Inhibiting the key enzymes of this pathway (i.e. kynureninase and kynurenine 3-hydroxylase) would lower the QUIN/KYNA ratio, which may potentially have neuroprotective effects. We have developed high through-put assays for kynurenine pathway enzymes which allow us to screen extracts from marine organisms for selective enzyme inhibitors. Active metabolites are purified, isolated and identified by HPLC, high-field NMR and mass spectral techniques. Extracts from a sponge of the Aka species were found to contain a selective inhibitor of kynureninase. We have recently purified and identified the active principal as being serotonin sulfate. Related indoleamines, serotonin and 5-hydroxyindoleacetic acids are inactive. This finding may be suggestive of a novel interaction between the serotoninergic and excitatory amino acid pathways. 相似文献
66.
Grant RS Naif H Thuruthyil SJ Nasr N Littlejohn T Takikawa O Kapoor V 《Redox report : communications in free radical research》2000,5(2-3):105-107
Increased kynurenine pathway metabolism has been implicated in the aetiology of the AIDS dementia complex (ADC). The rate limiting enzyme for this pathway is indoleamine 2,3-dioxygenase (IDO). We tested the efficacy of different strains of HIV-1 (HIV1-BaL, HIV1-JRFL and HIV1-631) to induce IDO in cultured human monocyte-derived macrophages (MDM). A significant increase in both IDO protein and kynurenine synthesis was observed after 48 h in MDM infected with the brain derived HIV-1 isolates, laboratory adapted (LA) HIV1-JRFL, and primary isolate HIV1-631. In contrast, almost no kynurenine production or IDO protein was evident in MDM infected with the high replicating macrophage tropic LA strain, HIV1-BaL. The induction of IDO and kynurenine synthesis by HIV1-JRFL and HIV1-631 declined to baseline levels by day-8 post-infection. Together, these results indicate that only selected strains of HIV-1 are capable of inducing IDO synthesis and subsequent oxidative tryptophan catabolism in MDM. 相似文献
67.
Gastropathy and defense mechanisms in common bile duct ligated portal hypertensive rats 总被引:6,自引:0,他引:6
Kaur S Kaur U Tandon C Dhawan V Ganguly NK Majumdar S 《Molecular and cellular biochemistry》2000,203(1-2):79-85
Portal hypertensive gastropathy is associated with a broad spectrum of gastric mucosal damage inspite of decreased gastric acid secretion, suggestive of compromised endogenous protective mechanisms. To determine the mechanisms of damage in portal hypertensive gastropathy we measured lipid peroxidation, glutathione, antioxidant and lysosomal enzymes in gastric mucosal homogenates from male Wistar rats with elevated intrasplenic pulp pressure, eighteen days after common bile duct ligation. Thiobarbituric acid-reactive substances and lysosomal enzymes (-glucuronidase and acid phosphatase) were increased in the common bile duct ligated group as compared to the sham-operated group. The levels of antioxidant defense enzymes, superoxide dismutase, glutathione peroxidase, catalase and glutathione were decreased as compared to the sham-operated controls. Pre-operative vitamin E administration decreased mucosal lipid peroxidation increased the levels of antioxidant defense enzymes and lowered the lysosomal enzymes. The plasma vitamin E levels in this group were lower when compared to animals receiving it post-operatively. In conclusion, free radical and lysosomal enzyme mediated damage may play a role in portal hypertensive gastropathy. 相似文献
68.
Pulse radiolytically generated halogenated alkylperoxyl radicals, namely CCl3OO*, CBr3OO*, CHCl2OO*, CHBr2OO*, etc. have been employed for a study of the oxidation of beta-carotene in a quaternary microemulsion. All these halogenated alkylperoxyl radicals produce a radical cation (absorption maximum at 840 nm), either via the initial formation of an adduct (absorption maximum at 740 nm), or by direct reaction. There was a considerable blue shift of both absorption peaks in the present system as compared to those earlier reported in non-polar as well as in micellar media. An additional intense absorption peak at approximately 345 nm was noted at a longer time scale and was stable up to 5 ms. On irradiation with a large number of electron pulses, a stable product with an absorption maximum at 315 nm appeared. On excitation at 315 nm, this product gave a fluorescence spectrum with an emission maximum at 525 nm. The absorption and fluorescence spectra of the stable product compared with those of retinol; this was further confirmed by HPLC analysis. A suitable mechanism has been proposed. 相似文献
69.
Selection potential based on differential fertility and mortality has been computed for six tribal groups inhabiting different geo-climatic conditions, namely: Sahariya, Mina and Bhil of the State of Rajasthan, north-western India, and Munda, Santal and Lodha of the State of West Bengal, eastern India. Irrespective of the methodology, the total index of selection was found to be highest among Lodhas (0.668), followed by Sahariyas (0.524), Santals (0.462), Bhils (0.386), Mundas (0.353) and Minas (0.334). Incidentally, Lodha and Sahariya are two of the seventy-four notified primitive tribal groups of India, and these two study populations show the highest index of total selection, mainly because of a higher embryonic and postnatal mortality. The relative contribution of the fertility component to the index of total selection is higher than the corresponding mortality component in all tribal groups. The analysis of postnatal mortality components indicates that childhood mortality constitutes the bulk of postnatal mortality, suggesting that children under 5 years need better health care in these tribal groups. 相似文献
70.
Veena Prasad Asish Ray Chaudhuri Matthew Curcio Isao Tomita Fukutaro Mizuhashi Kyoji Murata Richard F. Ludueña 《The protein journal》1998,17(7):663-668
Tubulin, the subunit protein of microtubules, undergoes a time-dependent loss of functional properties known as decay. We
have previously shown that the drug 2-(4-fluorophenyl)-1-(2-chloro-3,5-dimethoxyphenyl)-3-methyl-6-phenyl-4(1H)-pyridinone (IKP104) accelerates decay, but that in the presence of colchicine, IKP104 becomes a stabilizer of tubulin. To
see if this is due to conformational effects specific to colchicine or simply to occupancy at the colchicine site, we examined
the effects of nocodazole and podophyllotoxin, two well-known competitive inhibitors of colchicine for binding to tubulin,
on IKP104’s acceleration of decay. We found that podophyllotoxin abolished IKP104’s accelerating effect and, like colchicine,
turned it into a stabilizer of tubulin. Nocodazole’s effects were similar to those of podophyllotoxin and colchicine, in that
it abolished IKP104-induced enhancement of decay; however, in the presence of nocodazole, IKP104 caused little or no stabilization
of tubulin. Since colchicine, nocodazole, and podophyllotoxin have very different interactions with tubulin, but all inhibit
the IKP104-induced enhancement of decay, our findings suggest that this inhibition arises from occupancy of the colchicine
site rather than from a direct conformational effect of these two drugs. 相似文献