全文获取类型
收费全文 | 1519篇 |
免费 | 82篇 |
国内免费 | 2篇 |
出版年
2024年 | 4篇 |
2023年 | 18篇 |
2022年 | 42篇 |
2021年 | 73篇 |
2020年 | 37篇 |
2019年 | 40篇 |
2018年 | 75篇 |
2017年 | 47篇 |
2016年 | 58篇 |
2015年 | 76篇 |
2014年 | 100篇 |
2013年 | 90篇 |
2012年 | 101篇 |
2011年 | 75篇 |
2010年 | 52篇 |
2009年 | 54篇 |
2008年 | 77篇 |
2007年 | 78篇 |
2006年 | 55篇 |
2005年 | 50篇 |
2004年 | 58篇 |
2003年 | 43篇 |
2002年 | 29篇 |
2001年 | 23篇 |
2000年 | 32篇 |
1999年 | 17篇 |
1998年 | 5篇 |
1997年 | 6篇 |
1996年 | 10篇 |
1995年 | 7篇 |
1994年 | 6篇 |
1993年 | 8篇 |
1992年 | 16篇 |
1991年 | 15篇 |
1990年 | 16篇 |
1989年 | 18篇 |
1988年 | 7篇 |
1987年 | 4篇 |
1986年 | 10篇 |
1985年 | 7篇 |
1984年 | 13篇 |
1983年 | 6篇 |
1981年 | 9篇 |
1980年 | 7篇 |
1977年 | 4篇 |
1975年 | 5篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1965年 | 2篇 |
排序方式: 共有1603条查询结果,搜索用时 15 毫秒
81.
Md. Golam Sharoar Md. Shahnawaz Md. Imamul Islam Vijay Sankar Ramasamy Song Yub Shin Il-Seon Park 《Archives of biochemistry and biophysics》2013
The aggregation of β-amyloid (Aβ) peptide from its monomeric to its fibrillar form importantly contributes to the development of Alzheimer’s disease. Here, we investigated the effects of Escherichia coli maltose binding protein (MBP), which has been previously used as a fusion protein, on Aβ42 fibrillization, in order to improve understanding of the self-assembly process and the cytotoxic mechanism of Aβ42. MBP, at a sub-stoichiometric ratio with respect to Aβ42, was found to have chaperone-like inhibitory effects on β-sheet fibril formation, due to the accumulation of Aβ42 aggregates by sequestration of active Aβ42 species as Aβ42-MBP complexes. Furthermore, MBP increased the lag time of Aβ42 polymerization, decreased the growth rate of fibril extension, and suppressed Aβ42 mediated toxicity in human neuroblastoma SH-SY5Y cells. It appears that MBP decreases the active concentration of Aβ42 by sequestering it as Aβ42-MBP complex, and that this sequestration suppresses ongoing nucleation and retards the growth rate of Aβ42 species required for fibril formation. We speculate that inhibition of the growth rate of potent Aβ42 species by MBP suppresses Aβ42-mediated toxicity in SH-SY5Y cells. 相似文献
82.
Shawn A. Christensen Andriy Nemchenko Eli Borrego Ian Murray Islam S. Sobhy Liz Bosak Stacy DeBlasio Matthias Erb Christelle A.M. Robert Kathy A. Vaughn Cornelia Herrfurth Jim Tumlinson Ivo Feussner David Jackson Ted C.J. Turlings Jurgen Engelberth Christian Nansen Robert Meeley Michael V. Kolomiets 《The Plant journal : for cell and molecular biology》2013,74(1):59-73
Fatty acid derivatives are of central importance for plant immunity against insect herbivores; however, major regulatory genes and the signals that modulate these defense metabolites are vastly understudied, especially in important agro‐economic monocot species. Here we show that products and signals derived from a single Zea mays (maize) lipoxygenase (LOX), ZmLOX10, are critical for both direct and indirect defenses to herbivory. We provide genetic evidence that two 13‐LOXs, ZmLOX10 and ZmLOX8, specialize in providing substrate for the green leaf volatile (GLV) and jasmonate (JA) biosynthesis pathways, respectively. Supporting the specialization of these LOX isoforms, LOX8 and LOX10 are localized to two distinct cellular compartments, indicating that the JA and GLV biosynthesis pathways are physically separated in maize. Reduced expression of JA biosynthesis genes and diminished levels of JA in lox10 mutants indicate that LOX10‐derived signaling is required for LOX8‐mediated JA. The possible role of GLVs in JA signaling is supported by their ability to partially restore wound‐induced JA levels in lox10 mutants. The impaired ability of lox10 mutants to produce GLVs and JA led to dramatic reductions in herbivore‐induced plant volatiles (HIPVs) and attractiveness to parasitoid wasps. Because LOX10 is under circadian rhythm regulation, this study provides a mechanistic link to the diurnal regulation of GLVs and HIPVs. GLV‐, JA‐ and HIPV‐deficient lox10 mutants display compromised resistance to insect feeding, both under laboratory and field conditions, which is strong evidence that LOX10‐dependent metabolites confer immunity against insect attack. Hence, this comprehensive gene to agro‐ecosystem study reveals the broad implications of a single LOX isoform in herbivore defense. 相似文献
83.
Deborah M. Ramsey Md. Amirul Islam Lynne Turnbull Rohan A. Davis Cynthia B. Whitchurch Shelli R. McAlpine 《Bioorganic & medicinal chemistry letters》2013,23(17):4862-4866
Described is the antibiotic activity of a marine natural product. Psammaplysin F (1) inhibited the growth of four Gram-positive strains by >80% at 50 μM, and the amine at position C-20 is responsible for the observed antibacterial activity. When tested against two strains of methicillin resistant Staphylococcus aureus (MRSA), the minimum inhibitory concentrations (MICs) for psammaplysin F (40–80 μM) were similar to the structurally-related alkaloid psammaplysin H (2). Psammaplysin F (1) increased membrane permeability by two to four-fold compared to psammaplysin H (2) or control-treated bacteria, respectively. Unlike psammaplysin H (2), we show that psammaplysin F (1) inhibits equal partitioning of DNA into each daughter cell, suggesting that this natural product is a unique prokaryotic cell division inhibitor. 相似文献
84.
Mehjabeen Hossain Dil Umme Salma Chowdhury Jacy Farhana Mohammed Touaha Akbar Ananya Chakraborty Shamima Islam Adnan Mannan 《Bioinformation》2013,9(4):187-192
Staphylococcus aureus is a gram positive bacterium, responsible for both community-acquired and hospital-acquired infection,
resulting in a mortality rate of 39%. 43.2% resistance to methicilin and emerging resistance to Fluroquinolone and Oxazolidinone,
have evoked the necessity of the establishment of alternative and effective therapeutic approach to treat this bacteria. In this
computational study, various database and online software are used to determine some specific targets of Staphylococcus aureus
N315 other than those used by Penicillin, Quinolone and Oxazolidinone. For this purpose, among 302 essential proteins, 101 nonhomologous
proteins were accrued and 64 proteins which are unique in several metabolic pathways of S. aureus were isolated by
using metabolic pathway analysis tools. Furthermore, 7 essentially unique enzymes involved in exclusive metabolic pathways were
revealed by this research, which can be potential drug target. Along with these important enzymes, 15 non-homologous proteins
located on membrane were identified, which can play a vital role as potential therapeutic targets for the future researchers. 相似文献
85.
Tuhidul Islam Noor Shad Bibi Rami Reddy Vennapusa Marcelo Fernandez‐Lahore 《Journal of molecular recognition : JMR》2013,26(8):341-350
Peptide affinity tags have become efficient tools for the purification of recombinant proteins from biological mixtures. The most commonly used ligands in this type of affinity chromatography are immobilized metal ions, proteins, antibodies, and complementary peptides. However, the major bottlenecks of this technique are still related to the ligands, including their low stability, difficulties in immobilization, and leakage into the final products. A model approach is presented here to overcome these bottlenecks by utilizing macroporous ceramic fluorapatite (CFA) as the stationary phase in chromatography and the CFA‐specific short peptides as tags. The CFA chromatographic materials act as both the support matrix and the ligand. Peptides that bind with affinity to CFA were identified from a randomized phage display heptapeptide library. A total of five rounds of phage selection were performed. A common N‐terminal sequence was found in two selected peptides: F4‐2 (KPRSMLH) and F5‐4 (KPRSVSG). The peptide F5‐4, displayed by more than 40% of the phages analyzed in the fifth round of selection, was subjected to further studies. Selectivity of the peptide for the chemical composition and morphology of CFA was assured by the adsorption studies. The dissociation constant, obtained from the F5‐4/CFA adsorption isotherm, was in the micromolar range, and the maximum capacity was 39.4 nmol/mg. The chromatographic behavior of the peptides was characterized on a CFA stationary phase with different buffers. Preferential affinity and specific retention properties suggest the possible application of the phage‐derived peptides as a tag in CFA affinity chromatography for enhancing the selective recovery of proteins. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
86.
Atiqul Islam Maurizio Labbate Steven P. Djordjevic Munirul Alam Aaron Darling Jacqueline Melvold Andrew J. Holmes Fatema T. Johura Alejandro Cravioto Ian G. Charles H. W. Stokes 《Open biology》2013,3(2)
Of the 200+ serogroups of Vibrio cholerae, only O1 or O139 strains are reported to cause cholera, and mostly in endemic regions. Cholera outbreaks elsewhere are considered to be via importation of pathogenic strains. Using established animal models, we show that diverse V. cholerae strains indigenous to a non-endemic environment (Sydney, Australia), including non-O1/O139 serogroup strains, are able to both colonize the intestine and result in fluid accumulation despite lacking virulence factors believed to be important. Most strains lacked the type three secretion system considered a mediator of diarrhoea in non-O1/O13 V. cholerae. Multi-locus sequence typing (MLST) showed that the Sydney isolates did not form a single clade and were distinct from O1/O139 toxigenic strains. There was no correlation between genetic relatedness and the profile of virulence-associated factors. Current analyses of diseases mediated by V. cholerae focus on endemic regions, with only those strains that possess particular virulence factors considered pathogenic. Our data suggest that factors other than those previously well described are of potential importance in influencing disease outbreaks. 相似文献
87.
Background
Mechanomyography (MMG) has been extensively applied in clinical and experimental practice to examine muscle characteristics including muscle function (MF), prosthesis and/or switch control, signal processing, physiological exercise, and medical rehabilitation. Despite several existing MMG studies of MF, there has not yet been a review of these. This study aimed to determine the current status on the use of MMG in measuring the conditions of MFs.Methodology/Principal Findings
Five electronic databases were extensively searched for potentially eligible studies published between 2003 and 2012. Two authors independently assessed selected articles using an MS-Word based form created for this review. Several domains (name of muscle, study type, sensor type, subject''s types, muscle contraction, measured parameters, frequency range, hardware and software, signal processing and statistical analysis, results, applications, authors'' conclusions and recommendations for future work) were extracted for further analysis. From a total of 2184 citations 119 were selected for full-text evaluation and 36 studies of MFs were identified. The systematic results find sufficient evidence that MMG may be used for assessing muscle fatigue, strength, and balance. This review also provides reason to believe that MMG may be used to examine muscle actions during movements and for monitoring muscle activities under various types of exercise paradigms.Conclusions/Significance
Overall judging from the increasing number of articles in recent years, this review reports sufficient evidence that MMG is increasingly being used in different aspects of MF. Thus, MMG may be applied as a useful tool to examine diverse conditions of muscle activity. However, the existing studies which examined MMG for MFs were confined to a small sample size of healthy population. Therefore, future work is needed to investigate MMG, in examining MFs between a sufficient number of healthy subjects and neuromuscular patients. 相似文献88.
89.
Respiratory Viruses Associated Hospitalization among Children Aged <5 Years in Bangladesh: 2010-2014
Nusrat Homaira Stephen P. Luby Kamal Hossain Kariul Islam Makhdum Ahmed Mustafizur Rahman Ziaur Rahman Repon C. Paul Mejbah Uddin Bhuiyan W. Abdullah Brooks Badrul Munir Sohel Kajal Chandra Banik Marc-Alain Widdowson Melisa Willby Mahmudur Rahman Joseph Bresee Katharine-Sturm Ramirez Eduardo Azziz-Baumgartner 《PloS one》2016,11(2)
Background
We combined hospital-based surveillance and health utilization survey data to estimate the incidence of respiratory viral infections associated hospitalization among children aged < 5 years in Bangladesh.Methods
Surveillance physicians collected respiratory specimens from children aged <5 years hospitalized with respiratory illness and residing in the primary hospital catchment areas. We tested respiratory specimens for respiratory syncytial virus, parainfluenza viruses, human metapneumovirus, influenza, adenovirus and rhinoviruses using rRT-PCR. During 2013, we conducted a health utilization survey in the primary catchment areas of the hospitals to determine the proportion of all hospitalizations for respiratory illness among children aged <5 years at the surveillance hospitals during the preceding 12 months. We estimated the respiratory virus-specific incidence of hospitalization by dividing the estimated number of hospitalized children with a laboratory confirmed infection with a respiratory virus by the population aged <5 years of the catchment areas and adjusted for the proportion of children who were hospitalized at the surveillance hospitals.Results
We estimated that the annual incidence per 1000 children (95% CI) of all cause associated respiratory hospitalization was 11.5 (10–12). The incidences per 1000 children (95% CI) per year for respiratory syncytial virus, parainfluenza, adenovirus, human metapneumovirus and influenza infections were 3(2–3), 0.5(0.4–0.8), 0.4 (0.3–0.6), 0.4 (0.3–0.6), and 0.4 (0.3–0.6) respectively. The incidences per 1000 children (95%CI) of rhinovirus-associated infections among hospitalized children were 5 (3–7), 2 (1–3), 1 (0.6–2), and 3 (2–4) in 2010, 2011, 2012 and 2013, respectively.Conclusion
Our data suggest that respiratory viruses are associated with a substantial burden of hospitalization in children aged <5 years in Bangladesh. 相似文献90.
Tor Paaske Utheim Rakibul Islam Ida G. Fostad Jon R. Eidet Amer Sehic Ole K. Olstad Darlene A. Dartt Edward B. Messelt May Griffith Lara Pasovic 《PloS one》2016,11(3)