全文获取类型
收费全文 | 4474篇 |
免费 | 466篇 |
国内免费 | 570篇 |
出版年
2024年 | 8篇 |
2023年 | 80篇 |
2022年 | 125篇 |
2021年 | 267篇 |
2020年 | 234篇 |
2019年 | 298篇 |
2018年 | 218篇 |
2017年 | 176篇 |
2016年 | 198篇 |
2015年 | 294篇 |
2014年 | 343篇 |
2013年 | 341篇 |
2012年 | 455篇 |
2011年 | 383篇 |
2010年 | 237篇 |
2009年 | 218篇 |
2008年 | 216篇 |
2007年 | 189篇 |
2006年 | 152篇 |
2005年 | 148篇 |
2004年 | 126篇 |
2003年 | 125篇 |
2002年 | 105篇 |
2001年 | 90篇 |
2000年 | 71篇 |
1999年 | 55篇 |
1998年 | 33篇 |
1997年 | 34篇 |
1996年 | 27篇 |
1995年 | 26篇 |
1994年 | 23篇 |
1993年 | 20篇 |
1992年 | 25篇 |
1991年 | 17篇 |
1990年 | 18篇 |
1989年 | 14篇 |
1988年 | 11篇 |
1987年 | 7篇 |
1985年 | 5篇 |
1983年 | 12篇 |
1982年 | 5篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1977年 | 4篇 |
1973年 | 6篇 |
1972年 | 11篇 |
1971年 | 7篇 |
1970年 | 7篇 |
1968年 | 7篇 |
1967年 | 4篇 |
排序方式: 共有5510条查询结果,搜索用时 15 毫秒
101.
102.
Ke Zhu Jianxun Yi Yajuan Xiao Yumei Lai Pingping Song Wei Zheng Hongli Jiao Jie Fan Chuanyue Wu Di Chen Jingsong Zhou Guozhi Xiao 《The Journal of biological chemistry》2015,290(13):8081-8094
There is an intimate relationship between muscle and bone throughout life. However, how alterations in muscle functions in disease impact bone homeostasis is poorly understood. Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease characterized by progressive muscle atrophy. In this study we analyzed the effects of ALS on bone using the well established G93A transgenic mouse model, which harbors an ALS-causing mutation in the gene encoding superoxide dismutase 1. We found that 4-month-old G93A mice with severe muscle atrophy had dramatically reduced trabecular and cortical bone mass compared with their sex-matched wild type (WT) control littermates. Mechanically, we found that multiple osteoblast properties, such as the formation of osteoprogenitors, activation of Akt and Erk1/2 pathways, and osteoblast differentiation capacity, were severely impaired in primary cultures and bones from G93A relative to WT mice; this could contribute to reduced bone formation in the mutant mice. Conversely, osteoclast formation and bone resorption were strikingly enhanced in primary bone marrow cultures and bones of G93A mice compared with WT mice. Furthermore, sclerostin and RANKL expression in osteocytes embedded in the bone matrix were greatly up-regulated, and β-catenin was down-regulated in osteoblasts from G93A mice when compared with those of WT mice. Interestingly, calvarial bone that does not load and long bones from 2-month-old G93A mice without muscle atrophy displayed no detectable changes in parameters for osteoblast and osteoclast functions. Thus, for the first time to our knowledge, we have demonstrated that ALS causes abnormal bone remodeling and defined the underlying molecular and cellular mechanisms. 相似文献
103.
Jian Xie Timothy Owen Ke Xia Ajay Vikram Singh Emiley Tou Lingyun Li Brigitte Arduini Hongmin Li Leo Q. Wan Brian Callahan Chunyu Wang 《The Journal of biological chemistry》2015,290(18):11591-11600
Zinc is an essential trace element with wide-ranging biological functions, whereas the Hedgehog (Hh) signaling pathway plays crucial roles in both development and disease. Here we show that there is a mechanistic link between zinc and Hh signaling. The upstream activator of Hh signaling, the Hh ligand, originates from Hh autoprocessing, which converts the Hh precursor protein to the Hh ligand. In an in vitro Hh autoprocessing assay we show that zinc inhibits Hh autoprocessing with a Ki of 2 μm. We then demonstrate that zinc inhibits Hh autoprocessing in a cellular environment with experiments in primary rat astrocyte culture. Solution NMR reveals that zinc binds the active site residues of the Hh autoprocessing domain to inhibit autoprocessing, and isothermal titration calorimetry provided the thermodynamics of the binding. In normal physiology, zinc likely acts as a negative regulator of Hh autoprocessing and inhibits the generation of Hh ligand and Hh signaling. In many diseases, zinc deficiency and elevated level of Hh ligand co-exist, including prostate cancer, lung cancer, ovarian cancer, and autism. Our data suggest a causal relationship between zinc deficiency and the overproduction of Hh ligand. 相似文献
104.
Chao Xu ) Ke Liu Hazem Ahmed Peter Loppnau Matthieu Schapira Jinrong Min 《The Journal of biological chemistry》2015,290(41):24902-24913
N6-Methyladenosine (m6A) is the most abundant internal modification in RNA and is specifically recognized by YT521-B homology (YTH) domain-containing proteins. Recently we reported that YTHDC1 prefers guanosine and disfavors adenosine at the position preceding the m6A nucleotide in RNA and preferentially binds to the GG(m6A)C sequence. Now we systematically characterized the binding affinities of the YTH domains of three other human proteins and yeast YTH domain protein Pho92 and determined the crystal structures of the YTH domains of human YTHDF1 and yeast Pho92 in complex with a 5-mer m6A RNA, respectively. Our binding and structural data revealed that the YTH domain used a conserved aromatic cage to recognize m6A. Nevertheless, none of these YTH domains, except YTHDC1, display sequence selectivity at the position preceding the m6A modification. Structural comparison of these different YTH domains revealed that among those, only YTHDC1 harbors a distinctly selective binding pocket for the nucleotide preceding the m6A nucleotide. 相似文献
105.
Acetylcholine Inhibits Tumor Necrosis Factor α Activated Endoplasmic Reticulum Apoptotic Pathway via EGFR‐PI3K Signaling in Cardiomyocytes 下载免费PDF全文
106.
107.
108.
109.
110.