全文获取类型
收费全文 | 300篇 |
免费 | 47篇 |
出版年
2022年 | 2篇 |
2021年 | 2篇 |
2020年 | 3篇 |
2019年 | 2篇 |
2018年 | 7篇 |
2017年 | 5篇 |
2016年 | 11篇 |
2015年 | 8篇 |
2014年 | 9篇 |
2013年 | 15篇 |
2012年 | 15篇 |
2011年 | 18篇 |
2010年 | 10篇 |
2009年 | 9篇 |
2008年 | 9篇 |
2007年 | 20篇 |
2006年 | 16篇 |
2005年 | 15篇 |
2004年 | 9篇 |
2003年 | 7篇 |
2002年 | 11篇 |
2001年 | 14篇 |
2000年 | 3篇 |
1999年 | 11篇 |
1998年 | 6篇 |
1997年 | 4篇 |
1996年 | 5篇 |
1995年 | 7篇 |
1993年 | 2篇 |
1992年 | 5篇 |
1991年 | 4篇 |
1990年 | 8篇 |
1989年 | 6篇 |
1988年 | 7篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1985年 | 5篇 |
1984年 | 6篇 |
1983年 | 5篇 |
1982年 | 5篇 |
1980年 | 2篇 |
1979年 | 4篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1971年 | 6篇 |
1970年 | 2篇 |
1949年 | 1篇 |
1948年 | 2篇 |
排序方式: 共有347条查询结果,搜索用时 15 毫秒
31.
32.
33.
Narayan S Carlson EM Cheng H Condon K Du H Eckley S Hu Y Jiang Y Kumar V Lewis BM Saxton P Schuck E Seletsky BM Tendyke K Zhang H Zheng W Littlefield BA Towle MJ Yu MJ 《Bioorganic & medicinal chemistry letters》2011,21(6):1634-1638
Eribulin mesylate is a newly approved treatment for locally advanced and metastatic breast cancer. We targeted oral bioavailability and efficacy against multidrug resistant (MDR) tumors for further work. The design, synthesis and evaluation of novel amine-containing analogs of eribulin mesylate are described in this part. Attenuation of basicity of the amino group(s) in the C32 side-chain region led to compounds with low susceptibility to PgP-mediated drug efflux. These compounds were active against MDR tumor cell lines in vitro and in xenograft models in vivo, in addition to being orally bioavailable. 相似文献
34.
Jackson RW LaPorte MG Herbertz T Draper TL Gaboury JA Rippin SR Patel R Chunduru SK Benetatos CA Young DC Burns CJ Condon SM 《Bioorganic & medicinal chemistry letters》2011,21(11):3227-3231
We describe the structure-activity relationship of the C7-position of pyrano[3,4-b]indole-based inhibitors of HCV NS5B polymerase. Further exploration of the allosteric binding site led to the discovery of the significantly more potent compounds 13 and 14. 相似文献
35.
36.
Manira Rayamajhi Elizabeth F. Redente Tracy V. Condon Mercedes Gonzalez-Juarrero David W.H. Riches Laurel L. Lenz 《Journal of visualized experiments : JoVE》2011,(51)
Phagocytic cells such as alveolar macrophages and lung dendritic cells (LDCs) continuously sample antigens from the alveolar spaces in the
lungs. LDCs, in particular, are known to migrate to the lung draining lymph nodes (LDLNs) where they present inhaled antigens to T cells initiating an
appropriate immune response to a variety of immunogens1,2. To model interactions between the lungs and airborne antigens in mice, antigens can be
administered intranasally1,3,4, intratracheally5 or as aerosols6. Delivery by each route involves distinct technical skills and limitations that need to be
considered before designing an experiment. For example, intranasal and aerosolized exposure delivers antigens to both the lungs and the upper respiratory
tract. Hence antigens can access the nasal associated lymphoid tissue (NALT)7, potentially complicating interpretation of the results. In addition, swallowing,
sneezing and the breathing rate of the mouse may also lead to inconsistencies in the doses delivered. Although the involvement of the upper respiratory tract may
be preferred for some studies, it can complicate experiments focusing on events specifically initiated in the lungs. In this setting, the intratracheal (i.t)
route is preferable as it delivers test materials directly into the lungs and bypasses the NALT. Many i.t injection protocols involve either blind intubation of the
trachea through the oral cavity or surgical exposure of the trachea to access the lungs. Herein, we describe a simple, consistent, non-surgical method for i.t
instillation. The opening of the trachea is visualized using a laryngoscope and a bent gavage needle is then inserted directly into the trachea to deliver the
innoculum. We also describe procedures for harvesting and processing of LDLNs and lungs for analysis of antigen trafficking by flow cytometry.Download video file.(48M, mov) 相似文献
37.
Background
The superior colliculus (SC) and lateral geniculate nucleus (LGN) are important subcortical structures for vision. Much of our understanding of vision was obtained using invasive and small field of view (FOV) techniques. In this study, we use non-invasive, large FOV blood oxygenation level-dependent (BOLD) fMRI to measure the SC and LGN''s response temporal dynamics following short duration (1 s) visual stimulation.Methodology/Principal Findings
Experiments are performed at 7 tesla on Sprague Dawley rats stimulated in one eye with flashing light. Gradient-echo and spin-echo sequences are used to provide complementary information. An anatomical image is acquired from one rat after injection of monocrystalline iron oxide nanoparticles (MION), a blood vessel contrast agent. BOLD responses are concentrated in the contralateral SC and LGN. The SC BOLD signal measured with gradient-echo rises to 50% of maximum amplitude (PEAK) 0.2±0.2 s before the LGN signal (p<0.05). The LGN signal returns to 50% of PEAK 1.4±1.2 s before the SC signal (p<0.05). These results indicate the SC signal rises faster than the LGN signal but settles slower. Spin-echo results support these findings. The post-MION image shows the SC and LGN lie beneath large blood vessels. This subcortical vasculature is similar to that in the cortex, which also lies beneath large vessels. The LGN lies closer to the large vessels than much of the SC.Conclusions/Significance
The differences in response timing between SC and LGN are very similar to those between deep and shallow cortical layers following electrical stimulation, which are related to depth-dependent blood vessel dilation rates. This combined with the similarities in vasculature between subcortex and cortex suggest the SC and LGN timing differences are also related to depth-dependent dilation rates. This study shows for the first time that BOLD responses in the rat SC and LGN following short duration visual stimulation are temporally different. 相似文献38.
Deception remains a hotly debated topic in evolutionary and behavioural research. Our understanding of what impedes or facilitates the use and detection of deceptive signals in humans is still largely limited to studies of verbal deception under laboratory conditions. Recent theoretical models of non-human behaviour have suggested that the potential outcome for deceivers and the ability of receivers to discriminate signals can effectively maintain their honesty. In this paper, we empirically test these predictions in a real-world case of human deception, simulation in soccer. In support of theoretical predictions in signalling theory, we show that cost-free deceit by soccer players decreases as the potential outcome for the signaller becomes more costly. We further show that the ability of receivers (referees) to detect deceptive signals may limit the prevalence of deception by soccer players. Our study provides empirical support to recent theoretical models in signalling theory, and identifies conditions that may facilitate human deception and hinder its detection. 相似文献
39.
Yunjiao Wang Pawel Paszek Caroline A Horton Douglas B Kell Michael RH White David S Broomhead Mark R Muldoon 《BMC systems biology》2011,5(1):23
Background
Sustained stimulation with tumour necrosis factor alpha (TNF-alpha) induces substantial oscillations—observed at both the single cell and population levels—in the nuclear factor kappa B (NF-kappa B) system. Although the mechanism has not yet been elucidated fully, a core system has been identified consisting of a negative feedback loop involving NF-kappa B (RelA:p50 hetero-dimer) and its inhibitor I-kappa B-alpha. Many authors have suggested that this core oscillator should couple to other oscillatory pathways. 相似文献40.
Type A and B RNase P RNAs are interchangeable in vivo despite substantial biophysical differences
下载免费PDF全文
![点击此处可从《EMBO reports》网站下载免费的PDF全文](/ch/ext_images/free.gif)
We show that structural type A and B bacterial ribonuclease P (RNase P) RNAs can fully replace each other in vivo despite the many reported differences in their biogenesis, biochemical/biophysical properties and enzyme function in vitro. Our findings suggest that many of the reported idiosyncrasies of type A and B enzymes either do not reflect the in vivo situation or are not crucial for RNase P function in vivo, at least under standard growth conditions. The discrimination of mature tRNA by RNase P, so far thought to prevent product inhibition of the enzyme in the presence of a large cellular excess of mature tRNA relative to the precursor form, is apparently not crucial for RNase P function in vivo. 相似文献