全文获取类型
收费全文 | 504篇 |
免费 | 41篇 |
出版年
2023年 | 3篇 |
2022年 | 7篇 |
2021年 | 12篇 |
2020年 | 10篇 |
2019年 | 7篇 |
2018年 | 17篇 |
2017年 | 13篇 |
2016年 | 14篇 |
2015年 | 26篇 |
2014年 | 31篇 |
2013年 | 38篇 |
2012年 | 47篇 |
2011年 | 39篇 |
2010年 | 25篇 |
2009年 | 18篇 |
2008年 | 20篇 |
2007年 | 26篇 |
2006年 | 19篇 |
2005年 | 10篇 |
2004年 | 16篇 |
2003年 | 16篇 |
2002年 | 10篇 |
2001年 | 7篇 |
2000年 | 7篇 |
1999年 | 5篇 |
1998年 | 2篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1993年 | 7篇 |
1992年 | 6篇 |
1991年 | 2篇 |
1990年 | 10篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1981年 | 6篇 |
1980年 | 3篇 |
1979年 | 7篇 |
1978年 | 6篇 |
1977年 | 5篇 |
1976年 | 4篇 |
1974年 | 4篇 |
1972年 | 6篇 |
1968年 | 3篇 |
1967年 | 2篇 |
1961年 | 2篇 |
1959年 | 1篇 |
排序方式: 共有545条查询结果,搜索用时 15 毫秒
91.
92.
93.
Background
We examined whether impaired renal function causes thickening of the aortic valve leaflets in hyperlipidemic apoE-knockout (apoE-/-) mice, and whether the putative effect on the aortic valves could be prevented by inhibiting the angiotensin-converting enzyme (ACE) with enalapril.Methods
Thickening of the aortic valve leaflets in apoE-/- mice was induced by producing mild or moderate chronic renal failure resulting from unilateral nephrectomy (1/2 NX, n = 18) or subtotal nephrectomy (5/6 NX, n = 22), respectively. Additionally, the 5/6 NX mice were randomized to no treatment (n = 8) or enalapril treatment (n = 13). The maximal thickness of each leaflet was measured from histological sections of the aortic roots.Results
Leaflet thickness was significantly greater in the 5/6 NX mice than in the 1/2 NX mice (P = 0.030) or the unoperated mice (P = 0.003). The 5/6 NX mice treated with enalapril had significantly thinner leaflets than did the untreated 5/6 NX mice (P = 0.014).Conclusion
Moderate uremia causes thickening of the aortic valves in apoE-/- mice, which can be attenuated by ACE inhibition. The nephrectomized apoE-/- mouse constitutes a new model for investigating the mechanisms of uremia-induced aortic valve disease, and also provides an opportunity to study its pharmacologic prevention. 相似文献94.
Biftu T Feng D Fisher M Liang GB Qian X Scribner A Dennis R Lee S Liberator PA Brown C Gurnett A Leavitt PS Thompson D Mathew J Misura A Samaras S Tamas T Sina JF McNulty KA McKnight CG Schmatz DM Wyvratt M 《Bioorganic & medicinal chemistry letters》2006,16(9):2479-2483
Compounds 10a (IC50 110 pM) and 21 (IC50 40 pM) are the most potent inhibitors of Eimeria tenella cGMP-dependent protein kinase activity reported to date and are efficacious in the in vivo antiparasitic assay when administered to chickens at 12.5 and 6.25 ppm levels in the feed. However, both compounds are positive in the Ames microbial mutagenesis assay which precludes them from further development as antiprotozoal agents in the absence of negative lifetime rodent carcinogenicity studies. 相似文献
95.
Feng D Fisher M Liang GB Qian X Brown C Gurnett A Leavitt PS Liberator PA Mathew J Misura A Samaras S Tamas T Schmatz DM Wyvratt M Biftu T 《Bioorganic & medicinal chemistry letters》2006,16(23):5978-5981
Compounds 10a-10d and 10i are very potent inhibitors of Eimeria tenella cGMP-dependent protein kinase (0.081-0.32 nM) and are very efficacious antiparasitic agents in vivo when administered to chickens at 12.5-25 ppm levels in the feed. 相似文献
96.
Anna Kusakiewicz‐Dawid Monika Porada Wioletta Ochędzan‐Siodłak Małgorzata A. Broda Maciej Bujak Dawid Siodłak 《Journal of peptide science》2017,23(9):716-726
A series of model compounds containing 3‐amino‐1H‐pyrazole‐5‐carboxylic acid residue with N‐terminal amide/urethane and C‐terminal amide/hydrazide/ester groups were investigated by using NMR, Fourier transform infrared, and single‐crystal X‐ray diffraction methods, additionally supported by theoretical calculations. The studies demonstrate that the most preferred is the extended conformation with torsion angles ? and ψ close to ±180°. The studied 1H‐pyrazole with N‐terminal amide/urethane and C‐terminal amide/hydrazide groups solely adopts this energetically favored conformation confirming rigidity of that structural motif. However, when the C‐terminal ester group is present, the second conformation with torsion angles ? and ψ close to ±180° and 0°, respectively, is accessible. The conformational equilibrium is observed in NMR and Fourier transform infrared studies in solution in polar environment as well as in the crystal structures of other related compounds. The observed conformational preferences are clearly related to the presence of intramolecular interactions formed within the studied residue. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
97.
Hageman J van Waarde MA Zylicz A Walerych D Kampinga HH 《The Biochemical journal》2011,435(1):127-142
Humans contain many HSP (heat-shock protein) 70/HSPA- and HSP40/DNAJ-encoding genes and most of the corresponding proteins are localized in the cytosol. To test for possible functional differences and/or substrate specificity, we assessed the effect of overexpression of each of these HSPs on refolding of heat-denatured luciferase and on the suppression of aggregation of a non-foldable polyQ (polyglutamine)-expanded Huntingtin fragment. Overexpressed chaperones that suppressed polyQ aggregation were found not to be able to stimulate luciferase refolding. Inversely, chaperones that supported luciferase refolding were poor suppressors of polyQ aggregation. This was not related to client specificity itself, as the polyQ aggregation inhibitors often also suppressed heat-induced aggregation of luciferase. Surprisingly, the exclusively heat-inducible HSPA6 lacks both luciferase refolding and polyQ aggregation-suppressing activities. Furthermore, whereas overexpression of HSPA1A protected cells from heat-induced cell death, overexpression of HSPA6 did not. Inversely, siRNA (small interfering RNA)-mediated blocking of HSPA6 did not impair the development of heat-induced thermotolerance. Yet, HSPA6 has a functional substrate-binding domain and possesses intrinsic ATPase activity that is as high as that of the canonical HSPA1A when stimulated by J-proteins. In vitro data suggest that this may be relevant to substrate specificity, as purified HSPA6 could not chaperone heat-unfolded luciferase but was able to assist in reactivation of heat-unfolded p53. So, even within the highly sequence-conserved HSPA family, functional differentiation is larger than expected, with HSPA6 being an extreme example that may have evolved to maintain specific critical functions under conditions of severe stress. 相似文献
98.
Dawid Moroń Piotr Skórka Magdalena Lenda El?bieta Ro?ej-Pabijan Marta Wantuch Joanna Kajzer-Bonk Waldemar Celary ?ukasz Emil Mielczarek Piotr Tryjanowski 《PloS one》2014,9(7)
Pollinating insect populations, essential for maintaining wild plant diversity and agricultural productivity, rely on (semi)natural habitats. An increasing human population is encroaching upon and deteriorating pollinator habitats. Thus the population persistence of pollinating insects and their associated ecosystem services may depend upon on man-made novel habitats; however, their importance for ecosystem services is barely understood. We tested if man-made infrastructure (railway embankments) in an agricultural landscape establishes novel habitats that support large populations of pollinators (bees, butterflies, hoverflies) when compared to typical habitats for these insects, i.e., semi-natural grasslands. We also identified key environmental factors affecting the species richness and abundance of pollinators on embankments. Species richness and abundance of bees and butterflies were higher for railway embankments than for grasslands. The occurrence of bare (non-vegetated) ground on embankments positively affected bee species richness and abundance, but negatively affected butterfly populations. Species richness and abundance of butterflies positively depended on species richness of native plants on embankments, whereas bee species richness was positively affected by species richness of non-native flowering plants. The density of shrubs on embankments negatively affected the number of bee species and their abundance. Bee and hoverfly species richness were positively related to wood cover in a landscape surrounding embankments. This is the first study showing that railway embankments constitute valuable habitat for the conservation of pollinators in farmland. Specific conservation strategies involving embankments should focus on preventing habitat deterioration due to encroachment of dense shrubs and maintaining grassland vegetation with patches of bare ground. 相似文献
99.
100.