全文获取类型
收费全文 | 2105篇 |
免费 | 90篇 |
国内免费 | 2篇 |
出版年
2022年 | 9篇 |
2021年 | 30篇 |
2020年 | 14篇 |
2019年 | 23篇 |
2018年 | 28篇 |
2017年 | 24篇 |
2016年 | 41篇 |
2015年 | 60篇 |
2014年 | 69篇 |
2013年 | 123篇 |
2012年 | 114篇 |
2011年 | 136篇 |
2010年 | 97篇 |
2009年 | 75篇 |
2008年 | 158篇 |
2007年 | 142篇 |
2006年 | 140篇 |
2005年 | 122篇 |
2004年 | 136篇 |
2003年 | 120篇 |
2002年 | 115篇 |
2001年 | 21篇 |
2000年 | 25篇 |
1999年 | 21篇 |
1998年 | 31篇 |
1997年 | 33篇 |
1996年 | 20篇 |
1995年 | 32篇 |
1994年 | 16篇 |
1993年 | 23篇 |
1992年 | 18篇 |
1991年 | 20篇 |
1990年 | 22篇 |
1989年 | 14篇 |
1988年 | 7篇 |
1987年 | 10篇 |
1986年 | 11篇 |
1985年 | 6篇 |
1984年 | 13篇 |
1983年 | 7篇 |
1982年 | 11篇 |
1980年 | 7篇 |
1979年 | 4篇 |
1978年 | 7篇 |
1977年 | 4篇 |
1976年 | 6篇 |
1971年 | 3篇 |
1970年 | 4篇 |
1966年 | 4篇 |
1965年 | 3篇 |
排序方式: 共有2197条查询结果,搜索用时 218 毫秒
61.
Naoyuki Tsuchida Toshiyuki Takagi Hiroshi Takahashi Toshitada Yoshihara Seiji Tobita Masashi Sonoyama 《生物化学与生物物理学报:生物膜》2021,1863(5):183569
The plasma membranes of archaea are abundant in macrocyclic tetraether lipids that contain a single or double long transmembrane hydrocarbon chains connecting the two glycerol backbones at both ends. In this study, a novel amacrocyclic bisphosphatidylcholine lipid bearing a single membrane-spanning octacosamethylene chain, 1,1’-O-octacosamethylene-2,2′-di-O-tetradecyl-bis-(sn-glycero)-3,3′-diphosphocholine (AC-(di-O-C14PC)2), was synthesized to elucidate effects of the interlayer cross-linkage on membrane properties based on comparison with its corresponding diether phosphatidylcholine, 1,2-di-O-tetradecyl-sn-glycero-3-phosphocholine (DTPC), that forms bilayer membrane. Several physicochemical techniques demonstrated that while AC-(di-O-C14PC)2 monolayer, which adopts a particularly high-ordered structure in the gel phase, shows remarkably high thermotropic transition temperature compared to DTPC bilayer, the fluidity of both phospholipids above the transition temperature is comparable. Nonetheless, the fluorescent dye leakage from inside the AC-(di-O-C14PC)2 vesicles in the fluid phase is highly suppressed. The origin of the membrane properties characteristic of AC-(di-O-C14PC)2 monolayer is discussed in terms of the single long transmembrane hydrophobic linkage and the diffusional motion of the lipid molecules. 相似文献
62.
Noriaki Sasai Minori Kadoya Agnes Ong Lee Chen 《Development, growth & differentiation》2021,63(1):26-37
Embryonic stem (ES) cells are a useful experimental material to recapitulate the differentiation steps of early embryos, which are usually invisible and inaccessible from outside of the body, especially in mammals. ES cells have greatly facilitated the analyses of gene expression profiles and cell characteristics. In addition, understanding the mechanisms during neural differentiation is important for clinical purposes, such as developing new therapeutic methods or regenerative medicine. As neurons have very limited regenerative ability, neurodegenerative diseases are usually intractable, and patients suffer from the disease throughout their lifetimes. The functional cells generated from ES cells in vitro could replace degenerative areas by transplantation. In this review, we will first demonstrate the historical views and widely accepted concepts regarding the molecular mechanisms of neural induction and positional information to produce the specific types of neurons in model animals. Next, we will describe how these concepts have recently been applied to the research in the establishment of the methodology of neural differentiation from mammalian ES cells. Finally, we will focus on examples of the applications of differentiation systems to clinical purposes. Overall, the discussion will focus on how historical developmental studies are applied to state‐of‐the‐art stem cell research. 相似文献
63.
Seiji Tanaka 《Genetics》2021,217(1)
DNA replication in eukaryotes is a multi-step process that consists of three main reactions: helicase loading (licensing), helicase activation (firing), and nascent DNA synthesis (elongation). Although the contributions of some chromatin regulatory factors in the licensing and elongation reaction have been determined, their functions in the firing reaction remain elusive. In the budding yeast Saccharomyces cerevisiae, Sld3, Sld7, and Cdc45 (3–7–45) are rate-limiting in the firing reaction and simultaneous overexpression of 3–7–45 causes untimely activation of late and dormant replication origins. Here, we found that 3–7–45 overexpression not only activated dormant origins in the silenced locus, HMLα, but also exerted an anti-silencing effect at this locus. For these, interaction between Sld3 and Esa1, a conserved histone acetyltransferase, was responsible. Moreover, the Sld3–Esa1 interaction was required for the untimely activation of late origins. These results reveal the Sld3–Esa1 interaction as a novel level of regulation in the firing reaction. 相似文献
64.
65.
Mohammad Badrul Anam Arif Istiaq Ryusho Kariya Mikiko Kudo Shah Adil Ishtiyaq Ahmad Naofumi Ito Seiji Okada Kunimasa Ohta 《Biochemistry and Biophysics Reports》2021
Previously we reported that, lactic acid bacteria (LAB) can induce human dermal fibroblast (HDF) cells to form multipotent cell clusters which are able to transdifferentiate into three germ layer derived cell lineages. Later on, we confirmed that ribosome is responsible for the LAB-induced transdifferentiation and ribosomes from diverse organisms can mimic the LAB effect on HDF cells. In our present study we have shown that, upon incorporation of ribosomes, non-small cell lung cancer cell line A549 and gastric tubular adenocarcinoma cell line H-111-TC are transformed into spheroid like morphology those can be transdifferentiated into adipocytes and osteoblast. Our qPCR analysis has revealed that, during the formation of ribosome induced cancer cell spheroids, the expression of the cancer cell associated markers and cell cycle/proliferation markers were altered at different time point. Through our investigation, here we report a novel and a non-invasive approach for cancer cell reprogramming by incorporating ribosomes. 相似文献
66.
Yuichi Takashi Shun Sawatsubashi Itsuro Endo Yukiyo Ohnishi Masahiro Abe Munehide Matsuhisa Daiji Kawanami Toshio Matsumoto Seiji Fukumoto 《Biochemistry and Biophysics Reports》2021
Fibroblast growth factor (FGF) 23 produced by the bone is the principal hormone to regulate serum phosphate level. Serum FGF23 needs to be tightly regulated to maintain serum phosphate in a narrow range. Thus, we hypothesized that the bone has some phosphate-sensing mechanism to regulate the production of FGF23. Previously we showed that extracellular phosphate induces the phosphorylation of FGF receptor 1 (FGFR1) and FGFR1 signaling regulates the expression of Galnt3, whose product works to increase FGF23 production in vitro. In this study, we show the significance of FGFR1 in the regulated FGF23 production and serum phosphate level in vivo. We generated late-osteoblast/osteocyte-specific Fgfr1-knockout mice (Fgfr1fl/fl; OcnCre/+) by crossing the Ocn-Cre and the floxed Fgfr1 mouse lines. We evaluated serum phosphate and FGF23 levels, the expression of Galnt3 in the bone, the body weight and life span. A selective ablation of Fgfr1 aborted the increase of serum active full-length FGF23 and the enhanced expression of Galnt3 in the bone by a high phosphate diet. These mice showed more pronounced hyperphosphatemia compared with control mice. In addition, these mice fed with a control diet showed body weight loss after 23 weeks of age and shorter life span. These results reveal a novel significance of FGFR1 signaling in the phosphate metabolism and normal life span. 相似文献
67.
Saki Nagano-Koyashiki Makoto Matsubayashi Isao Kimata Masaru Furuya Hiroyuki Tani Kazumi Sasai 《Parasitology international》2013,62(2):109-111
Cryptosporidium andersoni is a protozoan parasite found in many countries that invades the stomachs of primarily adult cattle. Unlike the isolates of C. andersoni in cattle from other countries, C. andersoni isolates from Japanese cattle can infect mice and were identified as a novel type and later defined as C. andersoni Kawatabi type. The biological characteristics of C. andersoni Kawatabi type have not yet been well documented. In the present study, we assess the infectivity of this type isolate in mice with different immune competence status and age. We found that inoculation of more than 1 × 104 oocysts is needed to establish infection in mature mice irrespective of immune status. All of the infected immunocompetent mice recovered after a patent period of approximately 20 days. In immunodeficient mice, the pre-patent period was prolonged compared with that of 1 × 106 oocysts, but the pattern and the maximum shedding measured by the number of oocysts per day were almost identical. In neonatal immunocompetent and immunodeficient mice, inoculation with 1 × 104 to 105 oocysts was also needed to establish infection. Our results indicate that there is a threshold of oocysts needed to establish patent infection in the acidic conditions of the stomach. 相似文献
68.
69.
Seiji Hayashizaki Shinobu Hirai Yumi Ito Yoshiko Honda Yosefu Arime Ichiro Sora Haruo Okado Tohru Kodama Masahiko Takada 《PloS one》2013,8(10)
Dopamine regulates the psychomotor stimulant activities of amphetamine-like substances in the brain. The effects of dopamine are mediated through five known dopamine receptor subtypes in mammals. The functional relevance of D5 dopamine receptors in the central nervous system is not well understood. To determine the functional relevance of D5 dopamine receptors, we created D5 dopamine receptor-deficient mice and then used these mice to assess the roles of D5 dopamine receptors in the behavioral response to methamphetamine. Interestingly, D5 dopamine receptor-deficient mice displayed increased ambulation in response to methamphetamine. Furthermore, dopamine transporter threonine phosphorylation levels, which regulate amphetamine-induced dopamine release, were elevated in D5 dopamine receptor-deficient mice. The increase in methamphetamine-induced locomotor activity was eliminated by pretreatment with the dopamine transporter blocker GBR12909. Taken together, these results suggest that dopamine transporter activity and threonine phosphorylation levels are regulated by D5 dopamine receptors. 相似文献
70.
Kiyoshi Migita Toru Arai Naoki Ishizuka Yuka Jiuchi Yasuharu Sasaki Yasumori Izumi Tetsuyuki Kiyokawa Eiichi Suematsu Tomoya Miyamura Hiroshi Tsutani Yojiro Kawabe Ryutaro Matsumura Shunsuke Mori Shiro Ohshima Shigeru Yoshizawa Kenji Kawakami Yasuo Suenaga Hideo Nishimura Toyohiko Sugimoto Hiroaki Iwase Hideyuki Sawada Haruhiro Yamashita Shigeyuki Kuratsu Fumitaka Ogushi Masaharu Kawabata Toshihiro Matsui Hiroshi Furukawa Seiji Bito Shigeto Tohma 《PloS one》2013,8(11)