全文获取类型
收费全文 | 442篇 |
免费 | 31篇 |
国内免费 | 76篇 |
出版年
2024年 | 8篇 |
2023年 | 41篇 |
2022年 | 47篇 |
2021年 | 56篇 |
2020年 | 20篇 |
2019年 | 24篇 |
2018年 | 17篇 |
2017年 | 10篇 |
2016年 | 20篇 |
2015年 | 26篇 |
2014年 | 32篇 |
2013年 | 20篇 |
2012年 | 35篇 |
2011年 | 21篇 |
2010年 | 17篇 |
2009年 | 15篇 |
2008年 | 14篇 |
2007年 | 20篇 |
2006年 | 12篇 |
2005年 | 9篇 |
2004年 | 10篇 |
2003年 | 9篇 |
2002年 | 9篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 1篇 |
1998年 | 3篇 |
1997年 | 6篇 |
1996年 | 9篇 |
1995年 | 2篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1978年 | 1篇 |
1976年 | 1篇 |
1974年 | 1篇 |
1969年 | 2篇 |
排序方式: 共有549条查询结果,搜索用时 327 毫秒
51.
Background
Previously we reported 1 μM synthetic human amyloid beta1-42 oligomers induced cofilin dephosphorylation (activation) and formation of cofilin-actin rods within rat hippocampal neurons primarily localized to the dentate gyrus.Results
Here we demonstrate that a gel filtration fraction of 7PA2 cell-secreted SDS-stable human Aβ dimers and trimers (Aβd/t) induces maximal neuronal rod response at ~250 pM. This is 4,000-fold more active than traditionally prepared human Aβ oligomers, which contain SDS-stable trimers and tetramers, but are devoid of dimers. When incubated under tyrosine oxidizing conditions, synthetic human but not rodent Aβ1-42, the latter lacking tyrosine, acquires a marked increase (620 fold for EC50) in rod-inducing activity. Gel filtration of this preparation yielded two fractions containing SDS-stable dimers, trimers and tetramers. One, eluting at a similar volume to 7PA2 Aβd/t, had maximum activity at ~5 nM, whereas the other, eluting at the void volume (high-n state), lacked rod inducing activity at the same concentration. Fractions from 7PA2 medium containing Aβ monomers are not active, suggesting oxidized SDS-stable Aβ1-42 dimers in a low-n state are the most active rod-inducing species. Aβd/t-induced rods are predominantly localized to the dentate gyrus and mossy fiber tract, reach significance over controls within 2 h of treatment, and are reversible, disappearing by 24 h after Aβd/t washout. Overexpression of cofilin phosphatases increase rod formation when expressed alone and exacerbate rod formation when coupled with Aβd/t, whereas overexpression of a cofilin kinase inhibits Aβd/t-induced rod formation.Conclusions
Together these data support a mechanism by which Aβd/t alters the actin cytoskeleton via effects on cofilin in neurons critical to learning and memory. 相似文献52.
The malonato-bridged copper(II) complex [Cu(mal)(H2O)(azpy)1/2] · H2O (1) (mal = malonate, azpy = 4,4′-azobispyridine) has been synthesized and characterized by X-ray diffraction. The structure of 1 consists of malonato-bridged uniform copper(II) chains which are covalent connected through azpy to form two-dimensional wavelike network. The magnetic pathway of complex 1 is through a single syn-anti carboxylate bridge connecting equatorial and equatorial positions of adjacent copper(II) atoms, and have the value of the intrachain ferromagnetic coupling (J = 8.73(3) cm−1) and interchain antiferromagnetic coupling (zJ′ = − 1.31(1) cm−1) through a numerical expression for a ferromagnetic uniform chain. 相似文献
53.
Vogel CF Sciullo E Park S Liedtke C Trautwein C Matsumura F 《The Journal of biological chemistry》2004,279(10):8886-8894
54.
Study on rugose coral fauna of the Sifengya Formation (early Telychian) and Daluzhai Formation (mid-late Telychian) in Daguan
area, northeast Yunnan Province, China was carried out. Rugose coral fauna of the Sifengya Formation included 18 genera and
34 species, while Daluzhai Formation with nine genera, ten species. We described rugose coral fauna (12 genera, 19 species)
including one new genus and five new species, i.e. Protoketophyllum daguanense gen. et sp. nov., Crassilasma huanggexiense sp. nov., Pseudophaulactis heae sp. nov., P. convolutus sp. nov., and Shensiphyllum minor sp. nov. The characteristics and geological significance of rugose coral fauna of Sifengya Formation and Daluzhai Formation
were analyzed. Particularly, rugose coral fauna of the Sifengya Formation represent early Telychian rugosan fauna in the Upper
Yangtze region and improve the sequences of early Silurian (Llandovery) rugose coral assemblages in Yangtze region. It is
therefore very meaningful to further analyze radiation period of rugose coral fauna in such epoch.
__________
Translated from Acta Palaeontologica Sinica, 2005, 44(2): 229–246 [译自: 古生物学报, 2005, 44(2): 229–246] 相似文献
55.
56.
A decaprenyl diphosphate synthase gene (ddsA, GenBank accession No. DQ191802) was cloned from Rhodobacter capsulatus B10 by constructing and screening the genome library. An open reading frame of 1002 bp was revealed from sequence analysis. The deduced polypeptide consisted of 333 amino acids residues with an molecular mass of about 37 kDa. The DdsA protein contained the conserved amino acid sequence (DDXXD) of E-type polyprenyl diphosphate synthase and showed high similarity to others. In contrast, DdsA showed only 39% identity to a solanesyl diphosphate synthase cloned from R. capsulatus SB1003. DdsA was expressed successfully in Escherichia coli. Assaying the enzyme in vivo found it made E.coli synthesize UQ-10 in addition to the endogenous production UQ-8. 相似文献
57.
58.
59.
Yang XR Lin AH Hughes JM Flavahan NA Cao YN Liedtke W Sham JS 《American journal of physiology. Lung cellular and molecular physiology》2012,302(6):L555-L568
Chronic hypoxia causes pulmonary hypertension with vascular remodeling, increase in vascular tone, and altered reactivity to agonists. These changes involve alterations in multiple Ca(2+) pathways in pulmonary arterial smooth muscle cells (PASMCs). We have previously shown that vanilloid (TRPV)- and melastatin-related transient receptor potential (TRPM) channels are expressed in pulmonary arteries (PAs). Here we found that TRPV4 was the only member of the TRPV and TRPM subfamilies upregulated in PAs of chronic hypoxic rats. The increase in TRPV4 expression occurred within 1 day of hypoxia exposure, indicative of an early hypoxic response. TRPV4 in PASMCs were found to be mechanosensitive. Osmo-mechanical stress imposed by hypotonic solution activated Ca(2+) transients; they were inhibited by TRPV4 specific short interfering RNA, the TRPV blocker ruthenium red, and the cytochrome P450 epoxygenase inhibitor N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide. Consistent with TRPV4 upregulation, the Ca(2+) response induced by the TRPV4 agonist 4α-phorbol 12,13-didecanoate and hypotonicity was potentiated in hypoxic PASMCs. Moreover, a significant myogenic tone, sensitive to ruthenium red, was observed in pressurized endothelium denuded small PAs of hypoxic but not normoxic rats. The elevated basal intracellular Ca(2+) concentration in hypoxic PASMCs was also reduced by ruthenium red. In extension of these results, the development of pulmonary hypertension, right heart hypertrophy, and vascular remodeling was significantly delayed and suppressed in hypoxic trpv4(-/-) mice. These results suggest the novel concept that TRPV4 serves as a signal pathway crucial for the development of hypoxia-induced pulmonary hypertension. Its upregulation may provide a pathogenic feed-forward mechanism that promotes pulmonary hypertension via facilitated Ca(2+) influx, subsequently enhanced myogenic tone and vascular remodeling. 相似文献
60.
Jie Tian Jie Ma Ke Ma Bin Ma Xinyi Tang Samuel Essien Baidoo Jia Tong Jun Yan Liwei Lu Huaxi Xu Shengjun Wang 《PloS one》2012,7(10)