全文获取类型
收费全文 | 2105篇 |
免费 | 97篇 |
国内免费 | 3篇 |
出版年
2023年 | 12篇 |
2022年 | 24篇 |
2021年 | 46篇 |
2020年 | 36篇 |
2019年 | 39篇 |
2018年 | 46篇 |
2017年 | 29篇 |
2016年 | 62篇 |
2015年 | 86篇 |
2014年 | 97篇 |
2013年 | 140篇 |
2012年 | 142篇 |
2011年 | 179篇 |
2010年 | 89篇 |
2009年 | 83篇 |
2008年 | 105篇 |
2007年 | 105篇 |
2006年 | 106篇 |
2005年 | 101篇 |
2004年 | 78篇 |
2003年 | 72篇 |
2002年 | 71篇 |
2001年 | 35篇 |
2000年 | 31篇 |
1999年 | 34篇 |
1998年 | 17篇 |
1997年 | 14篇 |
1996年 | 12篇 |
1995年 | 17篇 |
1994年 | 11篇 |
1993年 | 15篇 |
1992年 | 26篇 |
1991年 | 20篇 |
1990年 | 17篇 |
1989年 | 20篇 |
1988年 | 23篇 |
1987年 | 15篇 |
1986年 | 14篇 |
1985年 | 17篇 |
1984年 | 11篇 |
1983年 | 10篇 |
1982年 | 11篇 |
1981年 | 10篇 |
1980年 | 10篇 |
1979年 | 8篇 |
1978年 | 9篇 |
1977年 | 8篇 |
1976年 | 6篇 |
1974年 | 9篇 |
1967年 | 5篇 |
排序方式: 共有2205条查询结果,搜索用时 187 毫秒
141.
The yeast Saccharomyces cerevisiae has two genes for α-tubulin, TUB1 and TUB3, and one β-tubulin gene, TUB2. The gene product of TUB3, Tub3, represents ~10% of α-tubulin in the cell. We determined the effects of the two α-tubulin isotypes on microtubule dynamics in vitro. Tubulin was purified from wild-type and deletion strains lacking either Tub1 or Tub3, and parameters of microtubule dynamics were examined. Microtubules containing Tub3 as the only α-tubulin isotype were less dynamic than wild-type microtubules, as shown by a shrinkage rate and catastrophe frequency that were about one-third of that for wild-type microtubules. Conversely, microtubules containing Tub1 as the only α-tubulin isotype were more dynamic than wild-type microtubules, as shown by a shrinkage rate that was 50% higher and a catastrophe frequency that was 30% higher than those of wild-type microtubules. The results suggest that a role of Tub3 in budding yeast is to control microtubule dynamics. 相似文献
142.
Recognition of cyclooxygenase-2 (COX-2) active site by NSAIDs: a computer modelling study 总被引:1,自引:0,他引:1
Kothekar V Sahi S Srinivasan M Mohan A Mishra J 《Indian journal of biochemistry & biophysics》2001,38(1-2):56-63
The energetics and models of COX-2 complexed with nonsteroidal anti-inflammatory drugs (NSAIDs) having different degrees of selectivity for two isoforms of COX (COX-2 and COX-1) have been studied using computer modelling approach. The models are obtained for complexes of NS398 (NS), a selective COX-2 inhibitor; indoprofen (Ind), a non-selective inhibitor; di-tert-butylbenzofurans (DHDMBFs) with substituents at the 5th position: CONH(CH2)2OMe (BF1), CONH-c-Pr (BF2), 3-methylene-gamma-butyrolactonyl (BF3) and oxicams namely, meloxicam (Mel), piroxicam (Pir) and tenoxicam (Ten). These were optimized using molecular mechanics (MM) and molecular dynamics (MD) techniques. The binding energies and structures were compared with pharmacological parameters and available results with COX-1. In case of NS a larger difference in the binding energies between COX-2 and COX-1 was noticed as compared to that of Ind. It also had stronger interaction with His90 and Tyr355 which is considered important for COX-2 selectivity. There was a difference in the compactness at the channel entrance between COX-2 selective and non-selective ligands. Models with DHDMBFs and oxicams showed a similar correlation. The results were used to design a peptide inhibitor, Tyr-Arg-Cys-Ala-delta Phe-Cys (Pept) which could fit better in the COX-2 cavity. As per our MD simulation results this peptide inhibitor showed both higher activity and COX-2 selectivity. 相似文献
143.
144.
Effect of L-arginine-nitric oxide system on the metabolism of essential fatty acids in chemical-induced diabetes mellitus 总被引:2,自引:0,他引:2
Several studies have shown that the activities of delta-6-desaturase and delta-5-desaturase are depressed in experimental diabetes and in humans with insulin- and non-insulin-dependent diabetes mellitus (type I and type II diabetes mellitus respectively). Furthermore, treatment with insulin is known to correct the defects in desaturases in rats and humans with diabetes, especially in type I. In a recent study, we demonstrated that L-arginine and nitric oxide can prevent alloxan-induced beta cell damage, and the severity of diabetes, and restore the antioxidant status to near normal levels. But, no information is available as to the relationship between L-arginine-nitric oxide system and the metabolism of essential fatty acids in diabetes mellitus. In the present study, it was noted that the plasma levels of saturated fatty acids: stearic and palmitic were increased where as unsaturated fatty acids such as oleic, linoleic, gamma-linolenic and eicosapentaenoic acids (OA, LA, GLA and EPA respectively) were decreased in alloxan-induced diabetic rats. In the liver phospholipid (PL) fraction, GLA, DGLA (dihomo-GLA) and alpha-linolenic acid (ALA) were decreased in the alloxan-treated group; in the muscle PL fraction, LA, GLA and DGLA were low, whereas an increase in the saturated fatty acid content was noted. L-arginine (the precursor of nitric oxide) and sodium nitroprusside (a nitric oxide donor) treatment of alloxan-induced diabetic rats enhanced the levels of LA, GLA and DGLA. Further, nitric oxide synthase inhibitor, L-NMMA, prevented this beneficial action of L-arginine-nitric oxide system on essential fatty acid metabolism. The abnormalities in the essential fatty acid metabolism observed also reverted to normalcy following control of diabetes with insulin. These results indicate that nitric oxide can enhance the activities of delta-6- and delta-5 desaturases, which are depressed in diabetes, and suggests that there is a close interaction between L-arginine-nitric oxide system and the metabolism of essential fatty acids. 相似文献
145.
Dehairs F. Rao R. G. Chandra Mohan P. Raman A.V. Marguillier S. Hellings L. 《Hydrobiologia》2000,431(2-3):225-241
Stable carbon isotopic composition and C/N ratio were used to trace the input of carbon associated with mangrove litter into the estuary of the Godavari–Gautami delta system and Kakinada bay (Andhra Pradesh, India). Suspended organic matter in the mangrove channels was more depleted in 13C (average 13C = –24.5) than in Kakinada bay which showed 13C values for suspended matter (average 13C = –22.7) closer to those expected for marine phytoplankton. Suspended organic matter from mangrove channels was enriched in nitrogen (average C/N atom ratio 12.7) and 13C (average 13C = –24.5) relative to mangrove leaf litter, which had a C/N ratio of 75 and a 13C value of –28. Lowest C/N ratios for suspended matter were observed during southwest monsoon when rainfall was highest. Although in general, mangrove litter fall was also lower during this period, no clear correlation was observed between litter fall and C/N ratio of suspended matter. In general, the composition of suspended matter pointed towards phytoplankton as a major component. Isotopic composition of zooplankton suggested selective feeding on 13C-enriched, marine phytoplankton in open Kakinada bay and on 13C-depleted organic matter, such as estuarine phytoplankton and mangrove litter, in the mangrove channels. From the 13C signature, it appeared that mangrove carbon was present to some extent in zooplankton and macrofauna from the mangrove mudflats and channels, but the signal rapidly decreased in Kakinada bay. Nitrogen isotopic composition of zooplankton and macrofauna indicated a progressive enrichment of 15N away from the mangrove forest towards the northern part of Kakinada bay, in approach of Kakinada city. This is thought to reflect input of anthropogenic nitrogen enriched in 15N and subsequent uptake of this enriched nitrogen into the aquatic food chain. 相似文献
146.
Wound repair/regeneration is a genetically controlled, complex process. In order to identify candidate genes regulating fast wound repair/regeneration in soft-tissue, the temporal protein profile of the soft-tissue healing process was analyzed in the ear-punched tissue of regeneration strain MRL/MpJ-Fas(lpr) (MRL) mice and non-regeneration strain C57BL/6J(B6) mice using surface-enhanced laser desorption and ionization (SELDI) ProteinChip technology. Five candidate proteins were identified in which responses of MRL to the ear punch were 2-4-fold different compared to that of B6. Their corresponding genes were predicted using an antigen-antibody assay validated mass-based approach. Most of the predicted genes are known to play a role or are likely to play a role in the wound repair/regeneration. Of the five candidate proteins, the amount of the 23560 Da protein in the ear-punched tissue was significantly correlated with the rate of ear healing in six representative strains of mice, making it a good candidate for fast wound repair/regeneration. We speculate that the increased concentration of the 23560 Da protein in the wound tissue could stimulate the expression of various growth-promoting proteins and consequently speed up the wound repair/regeneration processes. Here, we have shown that examination of protein expression profile using SELDI technology, coupled with database search, is an alternative approach to search for candidate genes for wound repair/regeneration. This novel approach can be implemented in a variety of biological applications. 相似文献
147.
Ch. Mohan Rao B. Raman T. Ramakrishna K. Rajaraman D. Ghosh S. Datta V. D. Trivedi M. B. Sukhaswami 《International journal of biological macromolecules》1998,22(3-4)
α-Crystallin is a multimeric lenticular protein that has recently been shown to be expressed in several non-lenticular tissues as well. It is shown to prevent aggregation of non-native proteins as a molecular chaperone. By using a non-thermal aggregation model, we could show that this process is temperature-dependent. We investigated the chaperone-like activity of α-crystallin towards photo-induced aggregation of γ-crystallin, aggregation of insulin and on the refolding induced aggregation of β- and γ-crystallins. We observed that α-crystallin could prevent photo-aggregation of γ-crystallin and this chaperone-like activity of α-crystallin is enhanced several fold at temperatures above 30°C. This enhancement parallels the exposure of its hydrophobic surfaces as a function of temperature, probed using hydrophobic fluorescent probes such as pyrene and 8-anilinonaphthalene-1-sulfonate. We, therefore, concluded that α-crystallin prevents the aggregation of other proteins by providing appropriately placed hydrophobic surfaces; a structural transition above 30°C involving enhanced or re-organized hydrophobic surfaces of α-crystallin is important for its chaperone-like activity. We also addressed the issue of conformational aspects of target proteins and found that their aggregation prone molten globule states bind to α-crystallin. We trace these developments and discuss some new lines that suggest the role of tertiary structural aspects in the chaperone process. 相似文献
148.
P. Rama Mohan Reddy M.V. Swamy G. Seenayya 《World journal of microbiology & biotechnology》1998,14(1):89-94
Thermostable -amylase and pullulanase, secreted by the thermophilic anaerobic bacterium Clostridium thermosulfurogenes strain SV2, were purified by salting out with ammonium sulphate, DEAE-cellulose column chromatography, and gel filtration using Sephadex G-200. Maltose was identified as a major hydrolysis product of starch by -amylase, and maltotriose was identified as a major hydrolysis product of pullulan by pullulanase. The molecular masses of native -amylase and pullulanase were determined to be 180 and 100 kDa by gel filtration, and 210 and 80 kDa by SDS–PAGE, respectively. The temperature optima of purified -amylase and pullulanase were 70 and 75°C, respectively, and both enzymes were completely stable at 70°C for 2h. The presence of starch further increased the stability of both the enzymes to 80°C and both displayed a pH activity optimum of 6.0. The starch hydrolysis products formed by -amylase action had -anomeric form. 相似文献
149.
Plant homologue of human excision repair gene ERCC1 points to conservation of DNA repair mechanisms 总被引:5,自引:1,他引:4
Huiling Xu Ines Swoboda Prem L. Bhalla Anneke M. Sijbers Chongxin Zhao Engkok Ong Jan H. J. Hoeijmakers Mohan B. Singh 《The Plant journal : for cell and molecular biology》1998,13(6):823-829
Nucleotide excision repair (NER), a highly versatile DNA repair mechanism, is capable of removing various types of DNA damage including those induced by UV radiation and chemical mutagens. NER has been well characterized in yeast and mammalian systems but its presence in plants has not been reported. Here it is reported that a plant gene isolated from male germline cells of lily (Lilium longiflorum) shows a striking amino acid sequence similarity to the DNA excision repair proteins human ERCC1 and yeast RAD10. Homologous genes are also shown to be present in a number of taxonomically diverse plant genera tested, suggesting that this gene may have a conserved function in plants. The protein encoded by this gene is able to correct significantly the sensitivity to the cross-linking agent mitomycin C in ERCC1-deficient Chinese hamster ovary (CHO) cells. These findings suggest that the NER mechanism is conserved in yeast, animals and higher plants. 相似文献
150.
Chokkalingam Uvarani Karuppannan Arumugasamy Kumarasamy Chandraprakash Mathan Sankaran Athar Ata Palathurai Subramaniam Mohan 《化学与生物多样性》2015,12(3):358-370
Phytochemical investigation of the CHCl3 fraction of Swertia corymbosa resulted in the isolation of a new 3‐allyl‐2,8‐dihydroxy‐1,6‐dimethoxy‐9H‐xanthen‐9‐one ( 1 ), along with four known xanthones, gentiacaulein ( 3 ), norswertianin ( 4 ), 1,3,6,8‐tetrahydroxyxanthone ( 5 ), and 1,3‐dihydroxyxanthone ( 6 ). Structure of compound 1 was elucidated with the aid of IR, UV, NMR, and MS data, and chemical transformation via new allyloxy xanthone derivative ( 2 ). Compounds 1 – 6 exhibited various levels of antioxidant and anti‐α‐glucosidase activities. Absorption and fluorescence spectroscopic studies on 1 – 6 indicated that these compounds could interact with calf thymus DNA (CT‐DNA) through intercalation and with bovine serum albumin (BSA) in a static quenching process. Compound 1 was found to be significantly cytotoxic against human cancer cell lines HeLa, HCT116, and AGS, and weakly active against normal NIH 3T3 cell line. 相似文献