全文获取类型
收费全文 | 708篇 |
免费 | 85篇 |
国内免费 | 18篇 |
出版年
2022年 | 14篇 |
2021年 | 22篇 |
2020年 | 12篇 |
2019年 | 14篇 |
2018年 | 12篇 |
2017年 | 12篇 |
2016年 | 23篇 |
2015年 | 41篇 |
2014年 | 37篇 |
2013年 | 44篇 |
2012年 | 47篇 |
2011年 | 35篇 |
2010年 | 34篇 |
2009年 | 32篇 |
2008年 | 29篇 |
2007年 | 23篇 |
2006年 | 20篇 |
2005年 | 20篇 |
2004年 | 10篇 |
2003年 | 17篇 |
2002年 | 18篇 |
2001年 | 21篇 |
2000年 | 20篇 |
1999年 | 14篇 |
1998年 | 16篇 |
1997年 | 8篇 |
1996年 | 7篇 |
1995年 | 4篇 |
1994年 | 7篇 |
1993年 | 5篇 |
1992年 | 4篇 |
1991年 | 5篇 |
1990年 | 5篇 |
1989年 | 10篇 |
1988年 | 8篇 |
1987年 | 7篇 |
1986年 | 5篇 |
1983年 | 4篇 |
1982年 | 8篇 |
1978年 | 6篇 |
1977年 | 7篇 |
1976年 | 6篇 |
1973年 | 4篇 |
1971年 | 6篇 |
1966年 | 4篇 |
1965年 | 6篇 |
1959年 | 4篇 |
1957年 | 4篇 |
1954年 | 4篇 |
1952年 | 4篇 |
排序方式: 共有811条查询结果,搜索用时 15 毫秒
101.
The hereditary spastic paraplegias (HSPs) are genetic conditions in which there is progressive axonal degeneration in the corticospinal tract. Autosomal dominant mutations, including nonsense, frameshift and missense changes, in the gene encoding the microtubule severing ATPase spastin are the most common cause of HSP in North America and northern Europe. In this study we report quantitative gait analysis using a motorized treadmill system, carried out on mice knocked-in for a disease-associated mutation affecting a critical residue in the Walker A motif of the spastin ATPase domain. At 4 months and at one year of age homozygous mutant mice had a number of abnormal gait parameters, including in stride length and stride duration, compared to heterozygous and wild-type littermates. Gait parameters in heterozygous animals did not differ from wild-type littermates. We conclude that quantitative gait analysis using the DigiGait system sensitively detects motor abnormalities in a hereditary spastic paraplegia model, and would be a useful method for analyzing the effects of pharmacological treatments for HSP. 相似文献
102.
103.
Thomas Wernberg Mads S. Thomsen Sean D. Connell Bayden D. Russell Jonathan M. Waters Giuseppe C. Zuccarello Gerald T. Kraft Craig Sanderson John A. West Carlos F. D. Gurgel 《PloS one》2013,8(11)
Explaining spatial patterns of biological organisation remains a central challenge for biogeographic studies. In marine systems, large-scale ocean currents can modify broad-scale biological patterns by simultaneously connecting environmental (e.g. temperature, salinity and nutrients) and biological (e.g. amounts and types of dispersed propagules) properties of adjacent and distant regions. For example, steep environmental gradients and highly variable, disrupted flow should lead to heterogeneity in regional communities and high species turnover. In this study, we investigated the possible imprint of the Leeuwin (LC) and East Australia (EAC) Currents on seaweed communities across ~7,000 km of coastline in temperate Australia. These currents flow poleward along the west and east coasts of Australia, respectively, but have markedly different characteristics. We tested the hypothesis that, regional seaweed communities show serial change in the direction of current flow and that, because the LC is characterised by a weaker temperature gradient and more un-interrupted along-shore flow compared to the EAC, then coasts influenced by the LC have less variable seaweed communities and lower species turnover across regions than the EAC. This hypothesis was supported. We suggest that this pattern is likely caused by a combination of seaweed temperature tolerances and current-driven dispersal. In conclusion, our findings support the idea that the characteristics of continental-scale currents can influence regional community organisation, and that the coupling of ocean currents and marine biological structure is a general feature that transcends taxa and spatial scales. 相似文献
104.
Hyun-Suk Lim M. Muralidhar Reddy Xiangshu Xiao Johnnie Wilson Rosemary Wilson Steven Connell Thomas Kodadek 《Bioorganic & medicinal chemistry letters》2009,19(14):3866-3869
A rapid array-based protocol is presented by which a modest affinity protein-binding small molecule can be appended to a library of peptoids via click chemistry. The array can then be screened for improved ligands that exhibit a higher affinity for the protein target. 相似文献
105.
Robert B. Lochhead James F. Zachary Luciana Dalla Rosa Ying Ma John H. Weis Ryan M. O’Connell Janis J. Weis 《PloS one》2015,10(8)
MicroRNA-155 has been shown to play a role in immune activation and inflammation, and is suppressed by IL-10, an important anti-inflammatory cytokine. The established involvement of IL-10 in the murine model of Borrelia burgdorferi-induced Lyme arthritis and carditis allowed us to assess the interplay between IL-10 and miR-155 in vivo. As reported previously, Mir155 was highly upregulated in joints from infected severely arthritic B6 Il10-/- mice, but not in mildly arthritic B6 mice. In infected hearts, Mir155 was upregulated in both strains, suggesting a role of miR-155 in Lyme carditis. Using B. burgdorferi-infected B6, Mir155-/-, Il10-/-, and Mir155-/- Il10-/- double-knockout (DKO) mice, we found that anti-inflammatory IL-10 and pro-inflammatory miR-155 have opposite and somewhat compensatory effects on myeloid cell activity, cytokine production, and antibody response. Both IL-10 and miR-155 were required for suppression of Lyme carditis. Infected Mir155-/- mice developed moderate/severe carditis, had higher B. burgdorferi numbers, and had reduced Th1 cytokine expression in hearts. In contrast, while Il10-/- and DKO mice also developed severe carditis, hearts had reduced bacterial numbers and elevated Th1 and innate cytokine expression. Surprisingly, miR-155 had little effect on Lyme arthritis. These results show that antagonistic interplay between IL-10 and miR-155 is required to balance host defense and immune activation in vivo, and this balance is particularly important for suppression of Lyme carditis. These results also highlight tissue-specific differences in Lyme arthritis and carditis pathogenesis, and reveal the importance of IL-10-mediated regulation of miR-155 in maintaining healthy immunity. 相似文献
106.
107.
108.
The initial steps in taste and olfaction result from the activation by
chemical stimuli of taste receptor cells (TRCs) and olfactory receptor
neurons (ORNs). In parallel with these two pathways is the chemosensitive
trigeminal pathway whose neurons terminate in the oral and nasal cavities
and which are activated by many of the same chemical stimuli that activate
TRCs and ORNs. In a recent single unit study we investigated the responses
of rat chorda tympani and glossopharnygeal neurons to a variety of
bitter-tasting alkaloids, including nicotine, yohimbine, quinine,
strychnine and caffeine, as well as capsaicin, the pungent ingredient in
hot pepper. Here we apply many of these same compounds to cultured rat
trigeminal ganglion (TG) neurons and measure changes in intracellular
calcium [Ca2+]i to determine whether TG neurons will respond to these same
compounds. Of the 89 neurons tested, 34% responded to 1 mM nicotine, 7% to
1 mM caffeine, 5% to 1 mM denatonium benzoate, 22% to 1 mM quinine
hydrochloride, 18% to 1 mM strychnine and 55% to 1 microM capsaicin. These
data suggest that neurons from the TG respond to the same bitter-tasting
chemical stimuli as do TRCs and are likely to contribute information sent
to the higher CNS regarding the perception of bitter/irritating chemical
stimuli.
相似文献
109.
110.