全文获取类型
收费全文 | 1184篇 |
免费 | 152篇 |
出版年
2022年 | 7篇 |
2021年 | 13篇 |
2020年 | 6篇 |
2018年 | 10篇 |
2017年 | 9篇 |
2016年 | 16篇 |
2015年 | 24篇 |
2014年 | 31篇 |
2013年 | 46篇 |
2012年 | 67篇 |
2011年 | 64篇 |
2010年 | 28篇 |
2009年 | 22篇 |
2008年 | 52篇 |
2007年 | 66篇 |
2006年 | 54篇 |
2005年 | 50篇 |
2004年 | 41篇 |
2003年 | 43篇 |
2002年 | 45篇 |
2001年 | 56篇 |
2000年 | 52篇 |
1999年 | 50篇 |
1998年 | 18篇 |
1997年 | 24篇 |
1996年 | 17篇 |
1995年 | 11篇 |
1994年 | 14篇 |
1993年 | 11篇 |
1992年 | 26篇 |
1991年 | 35篇 |
1990年 | 25篇 |
1989年 | 41篇 |
1988年 | 31篇 |
1987年 | 24篇 |
1986年 | 21篇 |
1985年 | 23篇 |
1984年 | 14篇 |
1983年 | 13篇 |
1982年 | 15篇 |
1980年 | 8篇 |
1979年 | 8篇 |
1978年 | 8篇 |
1977年 | 7篇 |
1976年 | 7篇 |
1975年 | 7篇 |
1974年 | 11篇 |
1973年 | 6篇 |
1971年 | 7篇 |
1968年 | 8篇 |
排序方式: 共有1336条查询结果,搜索用时 15 毫秒
141.
142.
Tatsuhisa Tsuboi Reina Yamazaki Risa Nobuta Ken Ikeuchi Shiho Makino Ayumi Ohtaki Yutaka Suzuki Tohru Yoshihisa Christopher Trotta Toshifumi Inada 《The Journal of biological chemistry》2015,290(26):16021-16030
The tRNA splicing endonuclease (Sen) complex is located on the mitochondrial outer membrane and splices precursor tRNAs in Saccharomyces cerevisiae. Here, we demonstrate that the Sen complex cleaves the mitochondria-localized mRNA encoding Cbp1 (cytochrome b mRNA processing 1). Endonucleolytic cleavage of this mRNA required two cis-elements: the mitochondrial targeting signal and the stem-loop 652–726-nt region. Mitochondrial localization of the Sen complex was required for cleavage of the CBP1 mRNA, and the Sen complex cleaved this mRNA directly in vitro. We propose that the Sen complex cleaves the CBP1 mRNA, which is co-translationally localized to mitochondria via its mitochondrial targeting signal. 相似文献
143.
144.
David J. Aceti Craig A. Bingman Russell L. Wrobel Ronnie O. Frederick Shin-ichi Makino Karl W. Nichols Sarata C. Sahu Lai F. Bergeman Paul G. Blommel Claudia C. Cornilescu Katarzyna A. Gromek Kory D. Seder Soyoon Hwang John G. Primm Grzegorz Sabat Frank C. Vojtik Brian F. Volkman Zsolt Zolnai George N. Phillips Jr. John L. Markley Brian G. Fox 《Journal of structural and functional genomics》2015,16(2):67-80
145.
Cytoglobin (Cgb) is a vertebrate heme‐containing globin‐protein expressed in a broad range of mammalian tissues. Unlike myoglobin, Cgb displays a hexa‐coordinated (bis‐hystidyl) heme iron atom, having the heme distal His81(E7) residue as the endogenous sixth ligand. In the present study, we crystallized human Cgb in the presence of a reductant Na2S2O4 under a carbon monoxide (CO) atmosphere, and determined the crystal structure at 2.6 Å resolution. The CO ligand occupies the sixth axial position of the heme ferrous iron. Eventually, the imidazole group of His81(E7) is expelled from the sixth position and swings out of the distal heme pocket. The flipping motion of the His81 imidazole group accompanies structural readjustments of some residues (Gln62, Phe63, Gln72, and Ser75) in both the CD‐corner and D‐helix regions of Cgb. On the other hand, no significant structural changes were observed in other Cgb regions, for example, on the proximal side. These structural alterations that occurred as a result of exogenous ligand (CO) binding are clearly different from those observed in other vertebrate hexa‐coordinated globins (mouse neuroglobin, Drosophila melanogaster hemoglobin) and penta‐coordinated sperm whale myoglobin. The present study provides the structural basis for further discussion of the unique ligand‐binding properties of Cgb. Proteins 2011. © 2011 Wiley‐Liss, Inc. 相似文献
146.
Yoshida M Mori A Morimoto S Kotani E Oka M Notoya K Makino H Ono M Shirasaki M Tada N Fujita H Ban J Ikeda Y Kawamoto T Goto M Kimura H Baba A Yasuma T 《Bioorganic & medicinal chemistry》2011,19(6):1881-1894
The calcium-sensing receptor antagonist (CaSR) has been recognized as a promising target of anabolic agents for treating osteoporosis. In the course of developing a new drug candidate for osteoporosis, we found tetrahydropyrazolopyrimidine derivative 1 to be an orally active CaSR antagonist that stimulated transient PTH secretion in rats. However, compound 1 showed poor physical and chemical stability. In order to work out this compound's chemical stability and further understand its in vivo efficacy, we focused on modifying the 2-position of the tetrahydropyrazolopyrimidine. As a result of chemical modification, we discovered (5R)-N-[1-ethyl-1-(4-ethylphenyl)propyl]-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide monotosylate 10m (TAK-075), which showed improved solubility, chemical stability, and in vivo efficacy. Furthermore, we describe that evaluating the active metabolite is important during repeated treatment with short-acting CaSR antagonists. 相似文献
147.
Fujimoto J Tanigawa K Kudo Y Makino H Watanabe K 《Journal of applied microbiology》2011,110(1):209-217
Aims: To develop a quick and accurate PCR‐based method to evaluate viable Bifidobacterium breve strain Yakult (BbrY) in human faeces. Methods and Results: The number of BbrY in faeces was detected by using strain‐specific quantitative real‐time PCR (qPCR) derived from a randomly amplified polymorphic DNA analysis. And using propidium monoazide (PMA) treatment, which combined a DNA‐intercalating dye for covalently linking DNA in dead cells and photoactivation, only viable BbrY in the faeces highly and significantly correlated with the number of viable BbrY added to faecal samples within the range of 105–109 cells per g of faeces was enumerated. After 11 healthy subjects ingested 10·7 log CFU of BbrY daily for 10 days, 6·9 (±1·5) log CFU g?1 [mean (±SD)] of BbrY was detected in faeces by using strain‐specific transgalactosylated oligosaccharide–carbenicillin (T‐CBPC) selective agar medium. Viable BbrY detected by qPCR with PMA treatment was 7·5 (±1·0) log cells per g and the total number (viable and dead) of BbrY detected by qPCR without PMA treatment was 8·1 (±0·8) log cells per g. Conclusions: Strain‐specific qPCR with PMA treatment evaluated viable BbrY in faeces quickly and accurately. Significance and Impact of the Study: Combination of strain‐specific qPCR and PMA treatment is useful for evaluating viable probiotics and its availability in humans. 相似文献
148.
149.
Combination of hTERT and bmi-1, E6, or E7 induces prolongation of the life span of bone marrow stromal cells from an elderly donor without affecting their neurogenic potential
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Mori T Kiyono T Imabayashi H Takeda Y Tsuchiya K Miyoshi S Makino H Matsumoto K Saito H Ogawa S Sakamoto M Hata J Umezawa A 《Molecular and cellular biology》2005,25(12):5183-5195
Murine bone marrow stromal cells differentiate not only into mesodermal derivatives, such as osteocytes, chondrocytes, adipocytes, skeletal myocytes, and cardiomyocytes, but also into neuroectodermal cells in vitro. Human bone marrow stromal cells are easy to isolate but difficult to study because of their limited life span. To overcome this problem, we attempted to prolong the life span of bone marrow stromal cells and investigated whether bone marrow stromal cells modified with bmi-1, hTERT, E6, and E7 retained their differentiated capability, or multipotency. In this study, we demonstrated that the life span of bone marrow stromal cells derived from a 91-year-old donor could be extended and that the stromal cells with an extended life span differentiated into neuronal cells in vitro. We examined the neuronally differentiated cells morphologically, physiologically, and biologically and compared the gene profiles of undifferentiated and differentiated cells. The neuronally differentiated cells exhibited characteristics similar to those of midbrain neuronal progenitors. Thus, the results of this study support the possible use of autologous-cell graft systems to treat central nervous system diseases in geriatric patients. 相似文献
150.