全文获取类型
收费全文 | 3052篇 |
免费 | 207篇 |
国内免费 | 2篇 |
专业分类
3261篇 |
出版年
2024年 | 2篇 |
2023年 | 24篇 |
2022年 | 43篇 |
2021年 | 90篇 |
2020年 | 55篇 |
2019年 | 59篇 |
2018年 | 95篇 |
2017年 | 62篇 |
2016年 | 115篇 |
2015年 | 164篇 |
2014年 | 160篇 |
2013年 | 225篇 |
2012年 | 277篇 |
2011年 | 253篇 |
2010年 | 169篇 |
2009年 | 139篇 |
2008年 | 226篇 |
2007年 | 178篇 |
2006年 | 191篇 |
2005年 | 132篇 |
2004年 | 128篇 |
2003年 | 127篇 |
2002年 | 118篇 |
2001年 | 23篇 |
2000年 | 9篇 |
1999年 | 22篇 |
1998年 | 14篇 |
1997年 | 16篇 |
1996年 | 15篇 |
1995年 | 21篇 |
1994年 | 16篇 |
1993年 | 10篇 |
1992年 | 15篇 |
1991年 | 8篇 |
1990年 | 4篇 |
1989年 | 8篇 |
1987年 | 6篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1983年 | 2篇 |
1982年 | 8篇 |
1981年 | 5篇 |
1980年 | 4篇 |
1975年 | 1篇 |
1974年 | 4篇 |
1972年 | 3篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1961年 | 1篇 |
1954年 | 1篇 |
排序方式: 共有3261条查询结果,搜索用时 15 毫秒
71.
72.
Ido Wolf Shiri Shahmoon Michal Ben Ami Yael Levy-Shraga Kineret Mazor-Aronovitch Orit Pinhas-Hamiel Yonatan Yeshayahu Rina Hemi Hannah Kanety Tami Rubinek Dalit Modan-Moses 《PloS one》2014,9(9)
Objective
Klotho is an aging-modulating protein expressed mainly in the kidneys and choroid plexus, which can also be shed, released into the circulation and act as a hormone. Klotho deficient mice are smaller compared to their wild-type counterparts and their somatotropes show marked atrophy and reduced number of secretory granules. Recent data also indicated an association between klotho levels and growth hormone (GH) levels in acromegaly. We aimed to study the association between klotho levels and GH deficiency (GHD) in children with growth impairment.Design
Prospective study comprising 99 children and adolescents (aged 9.0±3.7 years, 49 male) undergoing GH stimulation tests for short stature (height-SDS = −2.1±0.6). Klotho serum levels were measured using an α-klotho ELISA kit.Results
Klotho levels were significantly lower (p<0.001) among children with organic GHD (n = 11, 727±273 pg/ml) compared to both GH sufficient participants (n = 59, 1497±754 pg/ml) and those with idiopathic GHD (n = 29, 1645±778 pg/ml). The difference between GHS children and children with idiopathic GHD was not significant. Klotho levels positively correlated with IGF-1- standard deviation scores (SDS) (R = 0.45, p<0.001), but were not associated with gender, pubertal status, age or anthropometric measurements.Conclusions
We have shown, for the first time, an association between low serum klotho levels and organic GHD. If validated by additional studies, serum klotho may serve as novel biomarker of organic GHD. 相似文献73.
74.
75.
Telleria J Lafay B Virreira M Barnabé C Tibayrenc M Svoboda M 《Experimental parasitology》2006,114(4):279-288
The comparisons of 170 sequences of kinetoplast DNA minicircle hypervariable region obtained from 19 stocks of Trypanosoma cruzi and 2 stocks of Trypanosoma cruzi marenkellei showed that only 56% exhibited a significant homology one with other sequences. These sequences could be grouped into homology classes showing no significant sequence similarity with any other homology group. The 44% remaining sequences thus corresponded to unique sequences in our data set. In the DTU I ("Discrete Typing Units") 51% of the sequences were unique. In contrast, in the DTU IId, 87.5% of sequences were distributed into three classes. The results obtained for T. cruzi marinkellei, showed that all sequences were unique, without any similarity between them and T. cruzi sequences. Analysis of palindromes in all sequence sets show high frequency of the EcoRI site. Analysis of repetitive sequences suggested a common ancestral origin of the kDNA. The editing mechanism that occurs in kinetoplastidae is discussed. 相似文献
76.
77.
Calreticulin is a Ca2+-buffering ER chaperone that also modulates cell adhesiveness. In order to study the effect of calreticulin on the expression
of adhesion-related genes, we created a calreticulin inducible Human Embryonic Kidney (HEK) 293 cell line. We found that fibronectin
mRNA and both intra- and extra-cellular fibronectin protein levels increased following calreticulin induction. However, despite
this increase in fibronectin, HEK293 cells did not assemble an extracellular fibrillar fibronectin matrix regardless of the
level of calreticulin expression. Furthermore, HEK293 cells exhibited a poorly organized actin cytoskeleton, did not have
clustered fibronectin receptors at the cell surface, and did not form focal contacts. This likely accounts for the lack of
fibronectin matrix deposition by these cells regardless of calreticulin expression level. Vinculin abundance did not appreciably
increase upon calreticulin induction and the level of active c-Src, a regulatory kinase of focal contacts, was found to be
abundant and unregulated by calreticulin induction in these cells. The inability to form stable focal contacts and to commence
fibronectin fibrillogenesis due to high c-Src activity may be responsible for the poor adhesive phenotype of HEK 293 cells.
Thus, we show here that HEK293 cells are not suitable for microscopical studies of cell-substratum adhesions, but are best
suited for biochemical studies.
S. Papp and M. P. Fadel have contributed equally to this work. 相似文献
78.
Willis CK Menzies AK Boyles JG Wojciechowski MS 《Integrative and comparative biology》2011,51(3):364-373
White-nose syndrome (WNS) has caused alarming declines of North American bat populations in the 5 years since its discovery. Affected bats appear to starve during hibernation, possibly because of disruption of normal cycles of torpor and arousal. The importance of hydration state and evaporative water loss (EWL) for influencing the duration of torpor bouts in hibernating mammals recently led to "the dehydration hypothesis," that cutaneous infection of the wing membranes of bats with the fungus Geomyces destructans causes dehydration which in turn, increases arousal frequency during hibernation. This hypothesis predicts that uninfected individuals of species most susceptible to WNS, like little brown bats (Myotis lucifugus), exhibit high rates of EWL compared to less susceptible species. We tested the feasibility of this prediction using data from the literature and new data quantifying EWL in Natterer's bats (Myotis nattereri), a species that is, like other European bats, sympatric with G. destructans but does not appear to suffer significant mortality from WNS. We found that little brown bats exhibited significantly higher rates of normothermic EWL than did other bat species for which comparable EWL data are available. We also found that Natterer's bats exhibited significantly lower rates of EWL, in both wet and dry air, compared with values predicted for little brown bats exposed to identical relative humidity (RH). We used a population model to show that the increase in EWL required to cause the pattern of mortality observed for WNS-affected little brown bats was small, equivalent to a solitary bat hibernating exposed to RH of ~95%, or clusters hibernating in ~87% RH, as opposed to typical near-saturation conditions. Both of these results suggest the dehydration hypothesis is plausible and worth pursuing as a possible explanation for mortality of bats from WNS. 相似文献
79.
Hay-Koren A Caspi M Zilberberg A Rosin-Arbesfeld R 《Molecular biology of the cell》2011,22(3):399-411
Wnt/β-catenin signaling plays a central role in development and is also involved in a diverse array of diseases. β-Catenin activity is tightly regulated via a multiprotein complex that includes the kinase glycogen synthase kinase-3β (GSK-3β). GSK-3β phosphorylates β-catenin, marking it for ubiquitination and degradation via the proteasome. Thus in regulation of the Wnt pathway, the ubiquitin system is known to be involved mostly in mediating the turnover of β-catenin, resulting in reduced Wnt signaling levels. Here we report that an arm of the ubiquitin system increases β-catenin protein levels. We show that GSK-3β directly interacts with the E3 ubiquitin ligase identified by differential display (EDD) that also binds β-catenin. Expression of EDD leads to enhanced nuclear accumulation of both GSK-3β and β-catenin and results in up-regulation of β-catenin expression levels and activity. Importantly, EDD ubiquitinates β-catenin through Lys29- or Lys11-linked ubiquitin chains, leading to enhanced stability of β-catenin. Our results demonstrate a role for the ubiquitin system in up-regulation of the Wnt signaling pathway, suggesting that EDD could function as a colorectal oncogene. 相似文献
80.
Dukgyu Lee Tatsujiro Oka Beth Hunter Alison Robinson Sylvia Papp Kimitoshi Nakamura Wattamon Srisakuldee Barbara E. Nickel Peter E. Light Jason R. B. Dyck Gary D. Lopaschuk Elissavet Kardami Michal Opas Marek Michalak 《PloS one》2013,8(2)