全文获取类型
收费全文 | 422篇 |
免费 | 29篇 |
国内免费 | 3篇 |
出版年
2023年 | 6篇 |
2022年 | 1篇 |
2021年 | 8篇 |
2020年 | 5篇 |
2019年 | 17篇 |
2018年 | 14篇 |
2017年 | 13篇 |
2016年 | 18篇 |
2015年 | 26篇 |
2014年 | 24篇 |
2013年 | 27篇 |
2012年 | 25篇 |
2011年 | 30篇 |
2010年 | 18篇 |
2009年 | 22篇 |
2008年 | 21篇 |
2007年 | 20篇 |
2006年 | 18篇 |
2005年 | 17篇 |
2004年 | 14篇 |
2003年 | 12篇 |
2002年 | 8篇 |
2001年 | 12篇 |
2000年 | 7篇 |
1999年 | 4篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 5篇 |
1992年 | 4篇 |
1991年 | 2篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 5篇 |
1987年 | 6篇 |
1986年 | 4篇 |
1985年 | 5篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 1篇 |
排序方式: 共有454条查询结果,搜索用时 343 毫秒
91.
Abolghasem Tohidpour Shahin Najar Peerayeh Jalil F. Mehrabadi Hadi Rezaei Yazdi 《Current microbiology》2009,59(3):352-355
In Gram negative bacteria, fluoroquinolone resistance is acquired by target mutations in topoisomerase genes or by reducing
the permeation of drugs due to the increase in expression of endogenous multidrug efflux pumps that expel structurally unrelated
antimicrobial agents. An ongoing challenge is searching for new inhibitory substances in order to block efflux pumps and restore
the antibiotic drugs susceptibility. In this research, we sought to investigate the interplay between ciprofloxacin and an
efflux pump inhibitor (EPI), phenyl alanine arginyl β-naphtylamide (PAβN), to determine the prevalence of efflux pump overexpression
in clinical isolates of Pseudomonas aeruginosa. Ciprofloxacin was tested at different concentrations (256–0.25 μg/ml) with a fixed concentration of PAβN (50 μg/ml). The
isolates susceptibility profiles were analyzed by disc diffusion and agar dilution methods using 10 antibiotic discs and 4
powders. It was found that in the presence of PAβN, resistance to ciprofloxacin was inhibited obviously and MIC values were
decreased. The comparison between subgroups of P. aeruginosa isolates with different resistance profiles indicates that efflux pump overexpression (EPO) is present in 35% of ciprofloxacin
resistant isolates with no cross resistance and in variable frequencies among isolates showing cross resistance to other tested
antibiotics: gentamicin (31%), ceftazidime (29%), and imipenem (18%). Altogether, these results imply that PAβN maybe effective
to restore the fluoroquinolone drugs susceptibility in clinical treatment procedures. Results also show that increased use
of a fluoroquinolone drug such as ciprofloxacin can affect the susceptibility of P. aeruginosa to other different antipseudomonal agents. 相似文献
92.
93.
94.
Mark Burke Shahin Zangenehpour Peter R. Mouton Maurice Ptito 《Journal of visualized experiments : JoVE》2009,(27)
The non-human primate is an important translational species for understanding the normal function and disease processes of the human brain. Unbiased stereology, the method accepted as state-of-the-art for quantification of biological objects in tissue sections2, generates reliable structural data for biological features in the mammalian brain3. The key components of the approach are unbiased (systematic-random) sampling of anatomically defined structures (reference spaces), combined with quantification of cell numbers and size, fiber and capillary lengths, surface areas, regional volumes and spatial distributions of biological objects within the reference space4. Among the advantages of these stereological approaches over previous methods is the avoidance of all known sources of systematic (non-random) error arising from faulty assumptions and non-verifiable models. This study documents a biological application of computerized stereology to estimate the total neuronal population in the frontal cortex of the vervet monkey brain (Chlorocebus aethiops sabeus), with assistance from two commercially available stereology programs, BioQuant Life Sciences and Stereologer (Figure 1). In addition to contrast and comparison of results from both the BioQuant and Stereologer systems, this study provides a detailed protocol for the Stereologer system.Open in a separate windowClick here to view.(58M, flv) 相似文献
95.
Sarkandy SY Khalilzadeh R Shojaosadati SA Sadeghizadeh M Farnoud AM Babaeipour V Maghsoudi A 《Biotechnology and applied biochemistry》2010,57(4):151-156
A novel amino acid supplementation strategy was developed for enhancing the production of IL-2 (interleukin-2; as a model protein) by recombinant Escherichia coli BL21 (pET21a-hil2) in fed-batch high-cell-density cultures. The amino acids most needed and their amounts were determined using a stoichiometric model, and full factorial design experiments were conducted to determine the effects of single amino acids and amino acid mixtures on production. One of the most effective amino acid mixtures was found to be leucine, aspartic acid and glycine. This amino acid mixture was utilized for the production of IL-2 in batch and fed-batch fermentations. The amount of IL-2 produced increased from 403 to 722 mg/l and from 5.15 × 103 to 8.08 × 103 mg/l in batch and fed-batch cultures respectively. The results also revealed that the above amino acid mixture specifically increases IL-2 concentration in the cells. 相似文献
96.
Synaptotagmin I is the major Ca2+ sensor for membrane fusion during neurotransmitter release. The cytoplasmic domain of synaptotagmin consists of two C2 domains, C2A and C2B. On binding Ca2+, the tips of the two C2 domains rapidly and synchronously penetrate lipid bilayers. We investigated the forces of interaction between synaptotagmin and lipid bilayers using single-molecule force spectroscopy. Glutathione-S-transferase-tagged proteins were attached to an atomic force microscope cantilever via a glutathione-derivatized polyethylene glycol linker. With wild-type C2AB, the force profile for a bilayer containing phosphatidylserine had both Ca2+-dependent and Ca2+-independent components. No force was detected when the bilayer lacked phosphatidylserine, even in the presence of Ca2+. The binding characteristics of C2A and C2B indicated that the two C2 domains cooperate in binding synaptotagmin to the bilayer, and that the relatively weak Ca2+-independent force depends only on C2A. When the lysine residues K189-192 and K326, 327 were mutated to alanine, the strong Ca2+-dependent binding interaction was either absent or greatly reduced. We conclude that synaptotagmin binds to the bilayer via C2A even in absence of Ca2+, and also that positively charged regions of both C2A and C2B are essential for the strong Ca2+-dependent binding of synaptotagmin to the bilayer. 相似文献
97.
Vladimir Novitsky Rui Wang Hermann Bussmann Shahin Lockman Marianna Baum Roger Shapiro Ibou Thior Carolyn Wester C. William Wester Anthony Ogwu Aida Asmelash Rosemary Musonda Adriana Campa Sikhulile Moyo Erik van Widenfelt Madisa Mine Claire Moffat Mompati Mmalane Joseph Makhema Richard Marlink Peter Gilbert George R. Seage III Victor DeGruttola M. Essex 《PloS one》2010,5(4)
The first aim of the study is to assess the distribution of HIV-1 RNA levels in subtype C infection. Among 4,348 drug-naïve HIV-positive individuals participating in clinical studies in Botswana, the median baseline plasma HIV-1 RNA levels differed between the general population cohorts (4.1–4.2 log10) and cART-initiating cohorts (5.1–5.3 log10) by about one log10. The proportion of individuals with high (≥50,000 (4.7 log10) copies/ml) HIV-1 RNA levels ranged from 24%–28% in the general HIV-positive population cohorts to 65%–83% in cART-initiating cohorts. The second aim is to estimate the proportion of individuals who maintain high HIV-1 RNA levels for an extended time and the duration of this period. For this analysis, we estimate the proportion of individuals who could be identified by repeated 6- vs. 12-month-interval HIV testing, as well as the potential reduction of HIV transmission time that can be achieved by testing and ARV treating. Longitudinal analysis of 42 seroconverters revealed that 33% (95% CI: 20%–50%) of individuals maintain high HIV-1 RNA levels for at least 180 days post seroconversion (p/s) and the median duration of high viral load period was 350 (269; 428) days p/s. We found that it would be possible to identify all HIV-infected individuals with viral load ≥50,000 (4.7 log10) copies/ml using repeated six-month-interval HIV testing. Assuming individuals with high viral load initiate cART after being identified, the period of high transmissibility due to high viral load can potentially be reduced by 77% (95% CI: 71%–82%). Therefore, if HIV-infected individuals maintaining high levels of plasma HIV-1 RNA for extended period of time contribute disproportionally to HIV transmission, a modified “test-and-treat” strategy targeting such individuals by repeated HIV testing (followed by initiation of cART) might be a useful public health strategy for mitigating the HIV epidemic in some communities. 相似文献
98.
Jason M. Butler Daniel J. Nolan Eva L. Vertes Barbara Varnum-Finney Hideki Kobayashi Andrea T. Hooper Marco Seandel Koji Shido Ian A. White Mariko Kobayashi Larry Witte Chad May Carrie Shawber Yuki Kimura Jan Kitajewski Zev Rosenwaks Irwin D. Bernstein Shahin Rafii 《Cell Stem Cell》2010,6(3):251-264
Highlights? Coculture with endothelial cells promotes HSC expansion and self-renewal ? Endothelial cell effect on HSCs mediated by Notch signaling ? In vivo, sinusoidal endothelial cells (SECs) express Notch ligands ? Blocking vessel remodeling impairs hematopoietic recovery after irradiation 相似文献
99.
100.