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991.
Nayyar Rabbani Shams Tabrez Badar ul Islam Md Tabish Rehman Abdulrahman M. Alsenaidy Mohamed F. AlAjmi 《Journal of biomolecular structure & dynamics》2013,31(13):3453-3462
The transport of more than 90% of the drugs viz. anticoagulants, analgesics, and general anesthetics in the blood takes place by albumin. Hence, albumin is the prime protein needs to be investigated to find out the nature of drug binding. Serum albumin molecules are prone to glycation at elevated blood glucose levels as observed in diabetics. In this piece of work, glycation of bovine serum albumin (BSA) was carried out with glyceraldehyde and characterized by molecular docking and fluorometry techniques. Glycation of BSA showed 25% loss of free amino groups and decreased protein fluorescence (60%) with blue shift of 6 nm. The present study was also designed to evaluate the binding of colchicine (an anti-inflammatory drug) to native and glycated BSA and its ability to displace 8-analino-1-nephthalene sulfonic acid (ANS), from the BSA–ANS complex. Binding of ANS to BSA showed strong binding (Ka = 4.4 μM) with native conformation in comparison to glycated state (Ka = 8.4 μM). On the other hand, colchicine was able to quench the fluorescence of native BSA better than glycated BSA and also showed weaker affinity (Ka = 23 μM) for glycated albumin compared with native state (Ka = 16 μM). Molecular docking study showed that both glyceraldehyde and colchicine bind to common residues located near Sudlow’s site I that explain the lower binding of colchicine in the glycated BSA. Based on our results, we believe that reduced drugs-binding affinity to glycated albumin may lead to drugs accumulation and precipitation in diabetic patients. 相似文献
992.
Toru Arai Md. Ashraful Hoque Norikazu Nishino Hyun-Jung Kim Akihiro Ito Minoru Yoshida 《Amino acids》2013,45(4):835-843
Cyclic depsipeptide FK228 with an intramolecular disulfide bond is a potent inhibitor of histone deacetylases (HDAC). FK228 is stable in blood because of its prodrug function, whose –SS– bond is reduced within the cell. Here, cyclic peptides with –SS– bridges between a variety of amino acids were synthesized and assayed for HDAC inhibition. Cyclic peptide 3, cyclo(-l-amino acid-l-amino acid-l-Val-d-Pro-), with an –SS– bridge between the first and second amino acids, was found to be a potent HDAC inhibitor. Cyclic peptide 7, cyclo(-l-amino acid-d-amino acid-l-Val-d-Pro-), with an –SS– bridge between the first and second amino acids, was also a potent HDAC inhibitor. 相似文献
993.
Ahmed Kamal Shaikh Faazil M. Janaki Ramaiah Md. Ashraf M. Balakrishna S.N.C.V.L. Pushpavalli Nibedita Patel Manika Pal-Bhadra 《Bioorganic & medicinal chemistry letters》2013,23(20):5733-5739
By applying a methodology, a series of benzothiazole–pyrrole based conjugates (4a–r) were synthesized and evaluated for their antiproliferative activity. Compounds such as 4a, 4c, 4e, 4g–j, 4m, 4n, 4o and 4r exhibited significant cytotoxic effect in the MCF-7 cell line. Cell cycle effects were examined for these conjugates at 2 μM as well as 4 μM concentrations and FACS analysis show an increase of G2/M phase cells with concomitant decrease of G1 phase cells thereby indicating G2/M cell cycle arrest by them. Interestingly 4o and 4r are effective in causing apoptosis in MCF-7 cells. Moreover, 4o showed down regulation of oncogenic expression of Ras and its downstream effector molecules such as MEK1, ERK1/2, p38 MAPK and VEGF. The apoptotic aspect of this conjugate is further evidenced by increased expression of caspase-9 in MCF-7 cells. Hence these small molecules have the potential to control both the cell proliferation as well as the invasion process in the highly malignant breast cancers. 相似文献
994.
Ali Nakhi P.T.V.A. Srinivas Md. Shafiqur Rahman Ravada Kishore G.P.K. Seerapu K. Lalith Kumar Devyani Haldar M.V. Basaveswara Rao Manojit Pal 《Bioorganic & medicinal chemistry letters》2013,23(6):1828-1833
A rapid, inexpensive and high yielding method has been developed for the synthesis of 1,8-dioxodecahydroacridines using Amberlite IR-120H as a reusable catalyst under open air. These compounds were designed as potential inhibitors of sirtuins and prepared via the MCR of 5,5-dimethyl-1,3-cyclohexanedione, (hetero)aryl aldehydes and (hetero)aromatic amines under mild conditions. Further structure elaboration of a representative compound was performed via Pd catalyzed C–C bond forming reactions. The crystal structure analysis and H-bonding patterns along with in vitro inhibitory activity against yeast Sir2 of the same compound is presented. Docking studies indicated that the compound interacts well with the yeast Sir2. 相似文献
995.
Mohd. Basyaruddin Abdul Rahman Noor Mona Md Yunus Mohd Zobir Hussein Raja Noor Zaliha Raja Abdul Rahman Abu Bakar Salleh Mahiran Basri 《Biocatalysis and Biotransformation》2013,31(3-4):233-239
Ni/Al-layered double hydroxides (Ni-LDHs) and Ni/Al-sodium dodecyl sulfonate layered double hydroxide nanocomposites (Ni-SDS-LDHs) with a molar ratio of Ni:Al (4:1) have been prepared by a co-precipitation (or salt-base) method. Their structures were determined using Powder X-Ray Diffractometer (PXRD) and the spectra showed that basal spacings for Ni-LDHs and Ni-SDS-LDHs synthesised were around 8.1?Å and 34.8?Å, respectively. Lipase from Candida rugosa was immobilised onto these advanced materials, by physical adsorption. The activity of immobilised lipase was investigated through esterification of palmitic acid and isopropyl alcohol in hexane. The effects of reaction temperature, thermostability, stability in organic solvent, operational stability, leaching and storage studies of the immobilised lipase were investigated. These biocatalysts exhibited higher activities than the native lipase with an optimum temperature of 40°C. Immobilised lipases showed higher storage stability than native lipase (up to 60 days) and during operational studies at 30°C for 5?h, more than 50% of its activity was retained. Leaching studies showed that physical adsorption is suitable for the attachment of enzymes onto LDHs. 相似文献
996.
Che Salmah Md Rawi Salman Abdo Al-Shami Madziatul Rosemahanie Madrus Abu Hassan Ahmad 《Aquatic Ecology》2013,47(1):75-85
The influence of forest fragmentation (habitat isolation) on biological and ecological diversity of aquatic insects was investigated in streams of fragmented forests in Hulu Gombak (6 streams) and Gunung Angsi (5 streams) and un-fragmented forest of Berembun (6 streams) in peninsular Malaysia. Several environmental parameters including canopy cover, DO, temperature and pH differed significantly among the three catchments (P < 0.05). We found that taxonomic richness in Berembun forest was significantly different from Gunung Angsi (P < 0.05), but not with Hulu Gombak forests (P > 0.05). Nestedness pattern that measures the effect of habitat isolation on taxonomic assemblages showed that aquatic insect’s community in un-fragmented forest (Berembun) was less nested (T = 54.4), indicating high diversity compared to highly nested (less diverse) in the two fragmented forests (Hulu Gombak, T = 30.45 and Gunung Angsi, T = 35.45). Taxa similarity in Berembun streams was negatively correlated with the geographical distance among streams (Mantel test, r = ? 0.462, P < 0.05). Such correlation was absent in both Gunung Angsi and Hulu Gombak streams. Forest fragmentation in Hulu Gombak and Gunung Angsi measured as the distance of the forests from the nearest forested area had negative effect on aquatic insects diversity (r 2 = ? 0.149, P < 0.05), but not on their abundances (r 2 = 0.003, P > 0.05). We concluded that local habitat conditions were the most important in shaping the aquatic insects community among streams of both unfragmented and fragmented forests. 相似文献
997.
Noor Haza Fazlin Hashim Izwan Bharudin Douglas Law Sie Nguong Sakura Higa Farah Diba Abu Bakar Sheila Nathan Amir Rabu Hidehisa Kawahara Rosli Md. Illias Nazalan Najimudin Nor Muhammad Mahadi Abdul Munir Abdul Murad 《Extremophiles : life under extreme conditions》2013,17(1):63-73
The psychrophilic yeast Glaciozyma antarctica demonstrated high antifreeze activity in its culture filtrate. The culture filtrate exhibited both thermal hysteresis (TH) and ice recrystallization inhibition (RI) properties. The TH of 0.1 °C was comparable to that previously reported for bacteria and fungi. A genome sequence survey of the G. antarctica genome identified a novel antifreeze protein gene. The cDNA encoded a 177 amino acid protein with 30 % similarity to a fungal antifreeze protein from Typhula ishikariensis. The expression levels of AFP1 were quantified via real time-quantitative polymerase chain reaction (RT-qPCR), and the highest expression levels were detected within 6 h of growth at ?12 °C. The cDNA of the antifreeze protein was cloned into an Escherichia coli expression system. Expression of recombinant Afp1 in E. coli resulted in the formation of inclusion bodies that were subsequently denatured by treatment with urea and allowed to refold in vitro. Activity assays of the recombinant Afp1 confirmed the antifreeze protein properties with a high TH value of 0.08 °C. 相似文献
998.
Sam Tarrant Jeff Ollerton Md Lutfor Rahman Joanna Tarrant Duncan McCollin 《Restoration Ecology》2013,21(5):560-568
Pollinators are declining in Europe due to intensification of agriculture, habitat loss and fragmentation. Restored landfill sites are a significant potential reserve of semi‐natural habitat, so their conservation value for supporting populations of pollinating insects was here examined by assessing whether the plant and pollinator assemblages of restored landfill sites are comparable to reference sites of existing wildlife value. Floral characteristics of the vegetation and the species richness and abundance of flower‐visiting insect assemblages were compared between nine pairs of restored landfill sites and reference sites in the East Midlands of the United Kingdom, using standardized methods over two field seasons. No differences were found between the restored landfill and reference sites in terms of species richness or abundance of plants in flower and both types of site had similar assemblages of pollinators. However, plant and insect assemblages differed across the season, with species richness and abundance being lower for the restored landfill sites in the spring and higher in the autumn compared to the reference sites. The results indicate that in this region, landfill sites are being restored to a state comparable to that of the reference sites with regards to their provision of floral resources and the associated insect pollinator assemblages. Since there are currently 2,200 working landfill sites in England and Wales, covering 28,000 ha, and closing at a rate of 100 per year, this is potentially a significant reserve of land that could be restored. 相似文献
999.
Visceral leishmaniasis (VL) is caused by various species of the genus Leishmania. Internalization of Leishmania into host cells is facilitated by a large number of receptors, and therefore no panacea is available for the treatment of leishmaniasis. We previously demonstrated the requirement of host membrane cholesterol in the entry of Leishmania into macrophages by cholesterol depletion using methyl-β-cyclodextrin (MβCD). We recently showed that leishmanial infection is inhibited upon sequestration of host membrane cholesterol using amphotericin B (AmB), considered as the best existing drug against VL. The reason for the antileishmanial activity of AmB is generally believed to be its ability to bind ergosterol in parasite membranes. Our recent results offer the opportunity to reexamine the mechanism behind the effectiveness of current AmB-based therapeutic strategies to treat leishmaniasis. We propose here a novel mechanism in which the effectiveness of AmB treatment could be partly based on its ability to sequester cholesterol in the host membrane, thereby abrogating macrophage-parasite interaction. 相似文献
1000.
Kazuya Yamagata Takafumi Senokuchi Meihong Lu Makoto Takemoto Md. Fazlul Karim Chisa Go Yoshifumi Sato Mitsutoki Hatta Tatsuya Yoshizawa Eiichi Araki Junichi Miyazaki Wen-Jie Song 《Biochemical and biophysical research communications》2011,407(3):620
KCNQ1, located on 11p15.5, encodes a voltage-gated K+ channel with six transmembrane regions, and loss-of-function mutations in the KCNQ1 gene cause hereditary long QT syndrome. Recent genetic studies have identified that single nucleotide polymorphisms located in intron 15 of the KCNQ1 gene are strongly associated with type 2 diabetes and impaired insulin secretion. In order to understand the role of KCNQ1 in insulin secretion, we introduced KCNQ1 into the MIN6 mouse β-cell line using a retrovirus-mediated gene transfer system. In KCNQ1 transferred MIN6 cells, both the density of the KCNQ1 current and the density of the total K+ current were significantly increased. In addition, insulin secretion by glucose, pyruvate, or tolbutamide was significantly impaired by KCNQ1-overexpressing MIN6 cells. These results suggest that increased KCNQ1 protein expression limits insulin secretion from pancreatic β-cells by regulating the potassium channel current. 相似文献