全文获取类型
收费全文 | 395篇 |
免费 | 35篇 |
国内免费 | 1篇 |
出版年
2023年 | 3篇 |
2022年 | 4篇 |
2021年 | 6篇 |
2020年 | 3篇 |
2019年 | 3篇 |
2018年 | 18篇 |
2017年 | 18篇 |
2016年 | 19篇 |
2015年 | 10篇 |
2014年 | 18篇 |
2013年 | 33篇 |
2012年 | 31篇 |
2011年 | 35篇 |
2010年 | 16篇 |
2009年 | 13篇 |
2008年 | 24篇 |
2007年 | 17篇 |
2006年 | 17篇 |
2005年 | 8篇 |
2004年 | 12篇 |
2003年 | 13篇 |
2002年 | 10篇 |
2001年 | 2篇 |
2000年 | 2篇 |
1997年 | 4篇 |
1996年 | 5篇 |
1995年 | 9篇 |
1994年 | 3篇 |
1993年 | 5篇 |
1991年 | 7篇 |
1990年 | 2篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 6篇 |
1984年 | 5篇 |
1983年 | 1篇 |
1982年 | 3篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1979年 | 5篇 |
1978年 | 2篇 |
1977年 | 7篇 |
1976年 | 3篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1969年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有431条查询结果,搜索用时 171 毫秒
31.
Subbiyan Maruthasalam Ling Yin Shiu Murugan Loganathan Wei Ching Lien Yi Lun Liu Ching Mei Sun Chih Wen Yu Shu Hsien Hung Yeong Ko Chin Ho Lin 《Plant Growth Regulation》2010,60(2):83-90
Ethylene, a gaseous plant hormone, is responsible for the initiation of reproductive development in pineapple. Reproductive
development can be forced in pineapple (Ananas comosus var. comosus) throughout the year with ethylene. Inhibition of natural flowering initiation with aviglycine [(S)-trans-2-amino-4-(2-aminoethoxy)-3-butenoic acid hydrochloride], an inhibitor of ethylene biosynthesis, provides evidence
that reproductive development in response to cold stress and short daylength is also in response to ethylene production. We
studied the effect of cold treatment of pineapple on ethylene production and flower induction by applying a short-term cold
stress to stem apices. Shoot apices of pineapple treated with ice crystals also produced twice as much ethylene as did those
of control plants and significantly more than was produced by “D” leaf basal tissue. Moreover, pineapple plants treated four
times with ice crystals or ice water were induced to flower under field conditions and the forcing efficiency, as evaluated
by the percentages of inflorescence emergence and fruit harvest, was comparable to forcing with calcium carbide (CaC2) and ethephon. In another field experiment two applications of a 1.0% solution of CaC2 or 0.15% ethephon applied at 48 h intervals was sufficient to force reproductive development of ‘Tainon 17’. Furthermore,
0.5 or 1.0% solutions of CaC2 supplemented with 0.5% activated charcoal (AC) significantly improved the forcing effectiveness of CaC2. This could/would make it possible to reduce the number or concentration, or both, of CaC2 required to effect forcing in pineapple. 相似文献
32.
Immunization of primates with a Newcastle disease virus-vectored vaccine via the respiratory tract induces a high titer of serum neutralizing antibodies against highly pathogenic avian influenza virus 总被引:12,自引:3,他引:9
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
DiNapoli JM Yang L Suguitan A Elankumaran S Dorward DW Murphy BR Samal SK Collins PL Bukreyev A 《Journal of virology》2007,81(21):11560-11568
The ongoing outbreak of highly pathogenic avian influenza virus (HPAIV) in birds, the incidence of transmission to humans with a resulting high mortality rate, and the possibility of a human pandemic warrant the development of effective human vaccines against HPAIV. We developed an experimental live-attenuated vaccine for direct inoculation of the respiratory tract based on recombinant avian Newcastle disease virus (NDV) expressing the hemagglutinin (HA) glycoprotein of H5N1 HPAIV (NDV-HA). Expression of the HPAIV HA gene slightly reduced NDV virulence, as evidenced by the increased mean embryo death time and reduced replication in chickens. NDV-HA was administered to African green monkeys in two doses of 2 x 10(7) infectious units each with a 28-day interval to evaluate the systemic and local antibody responses specific to H5N1 HPAIV. The virus was shed only at low titers from the monkeys, indicative of safety. Two doses of NDV-HA induced a high titer of H5N1 HPAIV-neutralizing serum antibodies in all of the immunized monkeys. Moreover, a substantial mucosal immunoglobulin A response was induced in the respiratory tract after one and two doses. The titers of neutralizing antibodies achieved in this study suggest that the vaccine would be likely to prevent mortality and reduce morbidity caused by the H5N1 HPAIV. In addition, induction of a local immune response in the respiratory tract is an important advantage that is likely to reduce or prevent transmission of the virus during an outbreak or a pandemic. This vaccine is a candidate for clinical evaluation in humans. 相似文献
33.
Industrially important tannase producing fungi were isolated from tannery effluent using simple agar plate method. The isolates were screened by submerged fermentation using auto-controlled bioreactor. The colony diameter on the solid surface media shows high correlation with quantitative production of tannase. The isolate Aspergillus niger shows maximum production of both extracellular and intracellular enzyme. 相似文献
34.
Theoretical investigation on the glycan‐binding specificity of Agrocybe cylindracea galectin using molecular modeling and molecular dynamics simulation studies
下载免费PDF全文
![点击此处可从《Journal of molecular recognition : JMR》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Ponnusamy Parasuraman Veeramani Murugan Jeyasigamani F A Selvin M Michael Gromiha Kazuhiko Fukui Kasinadar Veluraja 《Journal of molecular recognition : JMR》2015,28(9):528-538
Galectins are β‐galactoside binding proteins which have the ability to serve as potent antitumor, cancer biomarker, and induce tumor cell apoptosis. Agrocybe cylindracea galectin (ACG) is a fungal galectin which specifically recognizes α(2,3)‐linked sialyllactose at the cell surface that plays extensive roles in the biological recognition processes. To investigate the change in glycan‐binding specificity upon mutations, single point and double point site‐directed in silico mutations are performed at the binding pocket of ACG. Molecular dynamics (MD) simulation studies are carried out for the wild‐type (ACG) and single point (ACG1) and double point (ACG2) mutated ACGs to investigate the dynamics of substituted mutants and their interactions with the receptor sialyllactose. Plausible binding modes are proposed for galectin–sialylglycan complexes based on the analysis of hydrogen bonding interactions, total pair‐wise interaction energy between the interacting binding site residues and sialyllactose and binding free energy of the complexes using molecular mechanics–Poisson–Boltzmann surface area. Our result shows that high contribution to the binding in different modes is due to the direct and water‐mediated hydrogen bonds. The binding specificity of double point mutant Y59R/N140Q of ACG2 is found to be high, and it has 26 direct and water‐mediated hydrogen bonds with a relatively low‐binding free energy of −47.52 ± 5.2 kcal/mol. We also observe that the substituted mutant Arg59 is crucial for glycan‐binding and for the preference of α(2,3)‐linked sialyllactose at the binding pocket of ACG2 galectin. When compared with the wild‐type and single point mutant, the double point mutant exhibits enhanced affinity towards α(2,3)‐linked sialyllactose, which can be effectively used as a model for biological cell marker in cancer therapeutics. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
35.
K. Murugan K. Selvanayaki Saleh Al-Sohaibani 《World journal of microbiology & biotechnology》2011,27(7):1661-1668
Respiratory tract and device associated infections caused by biofilm forming Pseudomonas aeruginosa play a primary role in the pathogenesis and prognosis of cystic fibrosis (CF) diseases. The biofilm formed by these pathogens
attributes to the antibiotic resistance and protection from host immune response. Once established, the pathogens respond
poorly to therapeutic agents. Recently medicinal plants are largely explored as potential source of bioactive agents. In this
context the present study reports the antibiofilm activity of the folkloric medicinal plant Andrographis paniculata against biofilm forming CF causative Pseudomonas aeruginosa isolated from CF sputum. P. aeruginosa was also assessed for their growth and development of the biofilm, phylogenetic relationship and antibiotic susceptibility.
Antibiogram of the strains indicated that they were resistant to more than one antibiotic. Six extracts of A. paniculata showed significant antibiofilm activity. P. aeruginosa strains, KMS P03 and KMS P05, were found to be maximally inhibited by the methanol extract to an extent of 88.6 and 87.5%
respectively. This is the first report on antibiofilm activity of A. paniculata extracts, and our results indicate scope for development of complementary medicine for biofilm associated infections. 相似文献
36.
Resveratrol (RES) and genistein (GEN) are the dietary natural products known to possess chemopreventive property and also the ability to repair DNA damage induced by mutagens/carcinogens. It is believed that the therapeutic activity of these compounds could be primarily due to their interaction with nucleic acids but detailed reports are not available. We here explore the interaction of these drugs with nucleic acids considering DNA and RNA as a potential therapeutic target. The interaction of RES and GEN has been analysed in buffered solution with DNA [saline sodium citrate (SSC)] and RNA [tris ethylene diammine tetra acetic acid (TE)] using UV-absorption and Fourier transform infrared (FTIR) spectroscopy. The UV analysis revealed lesser binding affinity with nucleic acids at lower concentration of RES (P/D = 5.00 and 10.00), while at higher drug concentration (P/D = 0.75, 1.00 and 2.50) hyperchromic effect with shift in the lambda(max) is noted for DNA and RNA. A major RES-nucleic acids complexes was observed through base pairs and phosphate backbone groups with K = 35.782 M(-1) and K = 34.25 M(-1) for DNARES and RNA-RES complexes respectively. At various concentrations of GEN (P/D = 0.25, 0.50, 0.75, 1.00 and 2.50) hyperchromicity with shift in the lambda(max) from 260-->263 nm and 260--> 270 nm is observed for DNA-GEN and RNA-GEN complexes respectively. The binding constant (from UV analysis) for GEN-nucleic acids complexes could not be obtained due to GEN absorbance overlap with that of nucleic acids at 260 nm. Nevertheless a detailed analysis with regard to the interaction of these drugs (RES/GEN) with DNA and RNA could feasibly be understood by FTIR. 相似文献
37.
The hemagglutinin-neuraminidase protein of Newcastle disease virus determines tropism and virulence 总被引:14,自引:0,他引:14
Huang Z Panda A Elankumaran S Govindarajan D Rockemann DD Samal SK 《Journal of virology》2004,78(8):4176-4184
The hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) plays a crucial role in the process of infection. However, the exact contribution of the HN gene to NDV pathogenesis is not known. In this study, the role of the HN gene in NDV virulence was examined. By use of reverse genetics procedures, the HN genes of a virulent recombinant NDV strain, rBeaudette C (rBC), and an avirulent recombinant NDV strain, rLaSota, were exchanged. The hemadsorption and neuraminidase activities of the chimeric viruses showed significant differences from those of their parental strains, but heterotypic F and HN pairs were equally effective in fusion promotion. The tissue tropism of the viruses was shown to be dependent on the origin of the HN protein. The chimeric virus with the HN protein derived from the virulent virus exhibited a tissue predilection similar to that of the virulent virus, and vice versa. The chimeric viruses with reciprocal HN proteins either gained or lost virulence, as determined by a standard intracerebral pathogenicity index test of chickens and by the mean death time in chicken embryos (a measure devised to classify these viruses), indicating that virulence is a function of the amino acid differences in the HN protein. These results are consistent with the hypothesis that the virulence of NDV is multigenic and that the cleavability of F protein alone does not determine the virulence of a strain. 相似文献
38.
Subbiah Elankumaran Vrushali Chavan Dan Qiao Raghunath Shobana Gopakumar Moorkanat Moanaro Biswas Siba K. Samal 《Journal of virology》2010,84(8):3835-3844
Newcastle disease virus (NDV), an avian paramyxovirus, is tumor selective and intrinsically oncolytic because of its potent ability to induce apoptosis. Several studies have demonstrated that NDV is selectively cytotoxic to tumor cells but not normal cells due to defects in the interferon (IFN) antiviral responses of tumor cells. Many naturally occurring strains of NDV have an intact IFN-antagonistic function and can still replicate in normal human cells. To avoid potential toxicity issues with NDV, especially in cancer patients with immunosuppression, safe NDV-oncolytic vectors are needed. We compared the cell killing abilities of (i) a recombinant NDV (rNDV) strain, Beaudette C, containing an IFN-antagonistic, wild-type V protein (rBC), (ii) an isogenic recombinant virus with a mutant V protein (rBC-Edit virus) that induces increased IFN in infected cells and whose replication is restricted in normal human cells, and (iii) a recombinant LaSota virus with a virulent F protein cleavage site that is as interferon sensitive as rBC-Edit virus (LaSota V.F. virus). Our results indicated that the tumor-selective replication of rNDV is determined by the differential regulation of IFN-α and downstream antiviral genes induced by IFN-α, especially through the IRF-7 pathway. In a nude mouse model of human fibrosarcoma, we show that the IFN-sensitive NDV variants are as effective as IFN-resistant rBC virus in clearing the tumor burden. In addition, mice treated with rNDV exhibited no signs of toxicity to the viruses. These findings indicate that augmentation of innate immune responses by NDV results in selective oncolysis and offer a novel and safe virotherapy platform.Several naturally occurring or engineered oncolytic viruses are emerging as novel tools for selective growth in and killing of a variety of tumor cells (1, 21, 34, 41). It has been consistently reported that during tumor evolution, diminished interferon (IFN) responsiveness coevolves as a frequent genetic defect (4, 31, 32, 41). Any defects in responsiveness to interferon will afford permissiveness of tumors for replication of oncolytic viruses by blunting the antiviral innate immune system. Thus, it was suggested that oncolytic viruses could be engineered to induce strong IFN response and/or to be defective in antagonizing the IFN signaling. This would result in virus replication in tumor cells with IFN defects but in reduced or crippled virus replication in normal cells, with the absence of toxicity (42). A variety of oncolytic viruses have been engineered to exploit tumor-specific genetic defects (3, 12, 24, 42, 46) and shown to be potent oncolytic agents.Newcastle disease virus (NDV), an avian paramyxovirus, is a promising broad-spectrum oncolytic agent (27, 29, 30, 37). Nonengineered, naturally occurring strains of NDV such as 73-T (6), MTH68 (7), PV701 (28, 35), and NDV-HUJ (11) have been successfully employed in several clinical studies for tumor regression. NDV is inherently oncolytic and tumor selective, sparing normal cells (9, 15, 37). The tumor selectivity of NDV is considered to be due to a defective IFN response in tumor cells (10, 23, 37). NDV is a strong inducer of type I IFN in many types of cells (18). In normal cells, a robust IFN-mediated antiviral response limits the replication of NDV (9, 23). This known sensitivity of NDV to cellular antiviral mechanisms affords a wide safety margin for its use in humans.Recent studies have indicated that improved therapeutic vectors of NDV could be engineered through reverse genetics for enhanced oncolytic efficacy from an increased anti-tumor response and interleukin 2 (IL-2) receptor-mediated targeting (5, 9, 44, 46). Therefore, we reasoned that recombinant NDVs (rNDVs) that are susceptible to cellular innate immune responses would be safer and more effective oncolytic agents. Even though NDV is an avian virus and induces a strong IFN response in normal human cells, it still expresses IFN-antagonizing activity. Ablation of the expression of V protein, which is responsible for this anti-IFN activity, may further reduce the ability of NDV to infect and kill normal human cells without affecting tumor cell infection and lysis. Here, we describe the relative oncolytic efficacies of three rNDV strains differing in IFN antagonism. The rNDV variants with an IFN-sensitive phenotype had parallel therapeutic efficacies in xenotransplanted human fibrosarcoma cells in a nude mouse model and offer great potential as recombinant vectors in therapy of human malignancies. 相似文献
39.
Brian J. Hawkins Krishna M. Irrinki Karthik Mallilankaraman Yu-Chin Lien Youjun Wang Cunnigaiper D. Bhanumathy Ramasamy Subbiah Michael F. Ritchie Jonathan Soboloff Yoshihiro Baba Tomohiro Kurosaki Suresh K. Joseph Donald L. Gill Muniswamy Madesh 《The Journal of cell biology》2010,190(3):391-405
Oxidant stress influences many cellular processes, including cell growth, differentiation, and cell death. A well-recognized link between these processes and oxidant stress is via alterations in Ca2+ signaling. However, precisely how oxidants influence Ca2+ signaling remains unclear. Oxidant stress led to a phenotypic shift in Ca2+ mobilization from an oscillatory to a sustained elevated pattern via calcium release–activated calcium (CRAC)–mediated capacitive Ca2+ entry, and stromal interaction molecule 1 (STIM1)– and Orai1-deficient cells are resistant to oxidant stress. Functionally, oxidant-induced Ca2+ entry alters mitochondrial Ca2+ handling and bioenergetics and triggers cell death. STIM1 is S-glutathionylated at cysteine 56 in response to oxidant stress and evokes constitutive Ca2+ entry independent of intracellular Ca2+ stores. These experiments reveal that cysteine 56 is a sensor for oxidant-dependent activation of STIM1 and demonstrate a molecular link between oxidant stress and Ca2+ signaling via the CRAC channel. 相似文献
40.