全文获取类型
收费全文 | 1094篇 |
免费 | 67篇 |
国内免费 | 1篇 |
出版年
2023年 | 13篇 |
2022年 | 36篇 |
2021年 | 57篇 |
2020年 | 23篇 |
2019年 | 22篇 |
2018年 | 42篇 |
2017年 | 43篇 |
2016年 | 41篇 |
2015年 | 77篇 |
2014年 | 75篇 |
2013年 | 98篇 |
2012年 | 110篇 |
2011年 | 102篇 |
2010年 | 56篇 |
2009年 | 48篇 |
2008年 | 60篇 |
2007年 | 54篇 |
2006年 | 48篇 |
2005年 | 35篇 |
2004年 | 32篇 |
2003年 | 33篇 |
2002年 | 30篇 |
2001年 | 5篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1997年 | 5篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1992年 | 1篇 |
1989年 | 1篇 |
1985年 | 1篇 |
1981年 | 1篇 |
排序方式: 共有1162条查询结果,搜索用时 15 毫秒
111.
112.
Hydrophobins are amphipathic self-assembling proteins secreted by filamentous fungi that exhibit remarkable ability to modify synthetic surfaces. Thin coatings of Sc3 hydrophobin isolated from the wood-rotting fungus Schizophyllum commune were prepared via spin coating and adsorption techniques onto polymeric surfaces. Surface morphology and nanotribological characteristics of the films were evaluated using lateral force microscopy (LFM) and nanoindentation techniques. This paper reports the first observation of reduction in nanoscale relative surface friction of Sc3 hydrophobin protein modified polymeric surfaces. Relative friction coefficients were dramatically reduced and hydrophilicity increased for polymer surfaces modified with Sc3 hydrophobin thin films. Morphology of the protein films as well as degree of surface modification was observed to be a function of film formation technique and composition of the substrate. 相似文献
113.
Lalit Kumar Vimal Kishore Manindra Bhushan Pawan Kumar Rahul Lal Chaudhary 《Reports of Practical Oncology and Radiotherapy》2021,26(4):582
BackgroundAcuros XB (AXB) may predict better rectal toxicities and treatment outcomes in cervix carcinoma. The aim of the study was to quantify the potential impact of AXB computations on the cervix radiotherapy using the RapidArc (RA ) technique as compared to anisotropic analytical algorithm (AA) computations.Materials and methodsA cohort of 30 patients previously cared for cervix carcinoma (stages II–IIIB) was selected for the present analysis. The RA plans were computed using AA and AXB dose computation engines under identical beam setup and MLC pattern.ResultsThere was no significant (p > 0.05) difference in D95% and D98% to the planning target volume (PTV); moreover, a significant (p < 0.05) rise was noticed for mean dose to the PTV (0.26%), D50% (0.26%), D2% (0.80%) and V110% (44.24%) for AXB computation as compared to AA computations. Further, AXB estimated a significantly (p < 0.05) lower value for maximum and minimum dose to the PTV. Additionally, there was a significant (p < 0.05) reduction observed in mean dose to organs at risk (OARs) for AXB computation as compared to AA, though the reduction in mean dose was non-significant (p > 0.05) for the rectum. The maximum difference observed was 4.78% for the rectum V50Gy, 1.72%, 1.15% in mean dose and 2.22%, 1.48% in D2% of the left femur and right femur, respectively, between AA and AXB dose estimations.ConclusionFor similar target coverage, there were significant differences observed between the AAA and AXB computations. AA underestimates the V50Gy of the rectum and overestimates the mean dose and D2% for femoral heads as compared to AXB. Therefore, the use of AXB in the case of cervix carcinoma may predict better rectal toxicities and treatment outcomes in cervix carcinoma using the RA technique. 相似文献
114.
The radiolabeled affinity and photoaffinity analogues of 25-hydroxyvitamin D(3) (25-OH-D(3)) with probes at the C-19 position failed to specifically label the 25-OH-D(3)-binding pocket of vitamin D-binding protein (DBP). However, a hybrid analogue, with a bromoacetate affinity probe and a photoaffinity probe at C(3)-OH and C(19) positions, respectively, specifically labeled the ligand-binding pocket, suggesting that C(3)-OH points towards the 'inside' of the binding cavity while the C(19) position faces away from it. 相似文献
115.
Lamour KH Mudge J Gobena D Hurtado-Gonzales OP Schmutz J Kuo A Miller NA Rice BJ Raffaele S Cano LM Bharti AK Donahoo RS Finley S Huitema E Hulvey J Platt D Salamov A Savidor A Sharma R Stam R Storey D Thines M Win J Haas BJ Dinwiddie DL Jenkins J Knight JR Affourtit JP Han CS Chertkov O Lindquist EA Detter C Grigoriev IV Kamoun S Kingsmore SF 《Molecular plant-microbe interactions : MPMI》2012,25(10):1350-1360
The oomycete vegetable pathogen Phytophthora capsici has shown remarkable adaptation to fungicides and new hosts. Like other members of this destructive genus, P. capsici has an explosive epidemiology, rapidly producing massive numbers of asexual spores on infected hosts. In addition, P. capsici can remain dormant for years as sexually recombined oospores, making it difficult to produce crops at infested sites, and allowing outcrossing populations to maintain significant genetic variation. Genome sequencing, development of a high-density genetic map, and integrative genomic or genetic characterization of P. capsici field isolates and intercross progeny revealed significant mitotic loss of heterozygosity (LOH) in diverse isolates. LOH was detected in clonally propagated field isolates and sexual progeny, cumulatively affecting >30% of the genome. LOH altered genotypes for more than 11,000 single-nucleotide variant sites and showed a strong association with changes in mating type and pathogenicity. Overall, it appears that LOH may provide a rapid mechanism for fixing alleles and may be an important component of adaptability for P. capsici. 相似文献
116.
Alam A Haldar S Thulasiram HV Kumar R Goyal M Iqbal MS Pal C Dey S Bindu S Sarkar S Pal U Maiti NC Bandyopadhyay U 《The Journal of biological chemistry》2012,287(29):24844-24861
Macrophage migration inhibitory factor (MIF) is responsible for proinflammatory reactions in various infectious and non-infectious diseases. We have investigated the mechanism of anti-inflammatory activity of epoxyazadiradione, a limonoid purified from neem (Azadirachta indica) fruits, against MIF. Epoxyazadiradione inhibited the tautomerase activity of MIF of both human (huMIF) and malaria parasites (Plasmodium falciparum (PfMIF) and Plasmodium yoelii (PyMIF)) non-competitively in a reversible fashion (K(i), 2.11-5.23 μm). Epoxyazadiradione also significantly inhibited MIF (huMIF, PyMIF, and PfMIF)-mediated proinflammatory activities in RAW 264.7 cells. It prevented MIF-induced macrophage chemotactic migration, NF-κB translocation to the nucleus, up-regulation of inducible nitric-oxide synthase, and nitric oxide production in RAW 264.7 cells. Epoxyazadiradione not only exhibited anti-inflammatory activity in vitro but also in vivo. We tested the anti-inflammatory activity of epoxyazadiradione in vivo after co-administering LPS and MIF in mice to mimic the disease state of sepsis or bacterial infection. Epoxyazadiradione prevented the release of proinflammatory cytokines such as IL-1α, IL-1β, IL-6, and TNF-α when LPS and PyMIF were co-administered to BALB/c mice. The molecular basis of interaction of epoxyazadiradione with MIFs was explored with the help of computational chemistry tools and a biological knowledgebase. Docking simulation indicated that the binding was highly specific and allosteric in nature. The well known MIF inhibitor (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) inhibited huMIF but not MIF of parasitic origin. In contrast, epoxyazadiradione inhibited both huMIF and plasmodial MIF, thus bearing an immense therapeutic potential against proinflammatory reactions induced by MIF of both malaria parasites and human. 相似文献
117.
V Jha P Chelikani X Carpena I Fita PC Loewen 《Archives of biochemistry and biophysics》2012,526(1):54-59
The main channel for H2O2 access to the heme cavity in large subunit catalases is twice as long as in small subunit catalases and is divided into two distinct parts. Like small subunit catalases, the 15 Å of the channel adjacent to the heme has a predominantly hydrophobic surface with only weak water occupancy, but the next 15 Å extending to the protein surface is hydrophilic and contains a complex water matrix in multiple passages. At the approximate junction of these two sections are a conserved serine and glutamate that are hydrogen bonded and associated with H2O2 in inactive variants. Mutation of these residues changed the dimensions of the channel, both enlarging and constricting it, and also changed the solvent occupancy in the hydrophobic, inner section of the main channel. Despite these structural changes and the prominent location of the residues in the channel, the variants exhibited less than a 2-fold change in the kcat and apparent KM kinetic constants. These results reflect the importance of the complex multi-passage structure of the main channel. Surprisingly, mutation of either the serine or glutamate to an aliphatic side chain interfered with heme oxidation to heme d. 相似文献
118.
Pal C Bindu S Dey S Alam A Goyal M Iqbal MS Sarkar S Kumar R Halder KK Debnath MC Adhikari S Bandyopadhyay U 《The Journal of biological chemistry》2012,287(5):3495-3509
We have investigated the gastroprotective effect of SEGA (3a), a newly synthesized tryptamine-gallic acid hybrid molecule against non-steroidal anti-inflammatory drug (NSAID)-induced gastropathy with mechanistic details. SEGA (3a) prevents indomethacin (NSAID)-induced mitochondrial oxidative stress (MOS) and dysfunctions in gastric mucosal cells, which play a pathogenic role in inducing gastropathy. SEGA (3a) offers this mitoprotective effect by scavenging of mitochondrial superoxide anion (O(2)(·-)) and intramitochondrial free iron released as a result of MOS. SEGA (3a) in vivo blocks indomethacin-mediated MOS, as is evident from the inhibition of indomethacin-induced mitochondrial protein carbonyl formation, lipid peroxidation, and thiol depletion. SEGA (3a) corrects indomethacin-mediated mitochondrial dysfunction in vivo by restoring defective electron transport chain function, collapse of transmembrane potential, and loss of dehydrogenase activity. SEGA (3a) not only corrects mitochondrial dysfunction but also inhibits the activation of the mitochondrial pathway of apoptosis by indomethacin. SEGA (3a) inhibits indomethacin-induced down-regulation of bcl-2 and up-regulation of bax genes in gastric mucosa. SEGA (3a) also inhibits indometacin-induced activation of caspase-9 and caspase-3 in gastric mucosa. Besides the gastroprotective effect against NSAID, SEGA (3a) also expedites the healing of already damaged gastric mucosa. Radiolabeled ((99m)Tc-labeled SEGA (3a)) tracer studies confirm that SEGA (3a) enters into mitochondria of gastric mucosal cell in vivo, and it is quite stable in serum. Thus, SEGA (3a) bears an immense potential to be a novel gastroprotective agent against NSAID-induced gastropathy. 相似文献
119.
Nelli RK Dunham SP Kuchipudi SV White GA Baquero-Perez B Chang P Ghaemmaghami A Brookes SM Brown IH Chang KC 《Journal of virology》2012,86(17):9201-9210
120.
Human chorionic gonadotropin (hCG) was initially believed to be secreted exclusively by the embryo with its primary function being "rescue" of the corpus luteum. However, recently it has been found that the hormone (or its individual subunits) is also secreted by many cancers and that in many cases secretion is associated with poor patient prognosis. In this study, we assessed the presence of hCG in colorectal cancer cells (CCL-253) and evaluated the anti-tumour effects of anti-hCG antibodies in vitro and in vivo. Anti-hCG antibodies were reactive with CCL-253, as revealed by confocal immunoflourescence microscopy; both cell surface and intracellular expression were observed. Western blot analysis showed that antibodies appeared to interact with several moieties, indicating a level of cross-reactivity. Anti-hCG antiserum specifically reduced the viability of tumor cells and the addition of complement increased in vitro anti-tumor effects. In nude mice implanted with CCL-253 cells, administration of anti-hCG antiserum caused a significant reduction in tumor volume; all treated animals survived, while mortality was observed in control animals. Results suggest that anti-hCG antibodies can mediate significant anti-tumor activity both in vitro and in vivo and lend support to the rationale of anti-hCG immunization in the therapy of gonadotropin- sensitive cancers. 相似文献