全文获取类型
收费全文 | 3642篇 |
免费 | 259篇 |
出版年
2022年 | 22篇 |
2021年 | 41篇 |
2020年 | 27篇 |
2019年 | 46篇 |
2018年 | 46篇 |
2017年 | 56篇 |
2016年 | 68篇 |
2015年 | 124篇 |
2014年 | 121篇 |
2013年 | 205篇 |
2012年 | 267篇 |
2011年 | 226篇 |
2010年 | 159篇 |
2009年 | 137篇 |
2008年 | 251篇 |
2007年 | 283篇 |
2006年 | 239篇 |
2005年 | 217篇 |
2004年 | 230篇 |
2003年 | 226篇 |
2002年 | 224篇 |
2001年 | 68篇 |
2000年 | 62篇 |
1999年 | 61篇 |
1998年 | 41篇 |
1997年 | 39篇 |
1996年 | 30篇 |
1995年 | 24篇 |
1994年 | 29篇 |
1993年 | 26篇 |
1992年 | 28篇 |
1991年 | 36篇 |
1990年 | 23篇 |
1989年 | 15篇 |
1988年 | 19篇 |
1987年 | 21篇 |
1986年 | 8篇 |
1985年 | 16篇 |
1984年 | 19篇 |
1983年 | 16篇 |
1982年 | 10篇 |
1981年 | 11篇 |
1980年 | 8篇 |
1979年 | 10篇 |
1978年 | 7篇 |
1977年 | 6篇 |
1976年 | 8篇 |
1975年 | 9篇 |
1973年 | 9篇 |
1972年 | 7篇 |
排序方式: 共有3901条查询结果,搜索用时 31 毫秒
101.
Shizuko Yamaguchi Tomoko Yoshikawa Shingo Ikeda Tsunehiko Ninomiya 《Bioscience, biotechnology, and biochemistry》2013,77(7):797-802
Taste effects of six newly synthesized ribonucleotide derivatives, i.e., disodium salts of 2-methyl-5′-inosinic acid · 6H2O, 2-ethyl-5′-inosinic acid · 1.5H2O, 2-N-methyl-5′-guanylic acid · 5.5H2O, 2-N-dimethyl-5′-guanylic acid · 2.5H2O, 2-methylthio-5′-inosinic acid · 6H2O and 2-ethylthio-5′-inosinic acid · 2H2O, were studied. Stimulus thresholds (detection thresholds) of these derivatives ranged from about 0.02 to 0.006 g/100ml. Flavor-enhancing activities of them were 2.3 to 8.0 times larger than that of disodium 5′-inosinate · 7.5H2O IMP) in the synergistic effect with monosodium glutamate. Furthermore, the quality of taste of all the derivatives was recognized to be the same kind to that of IMP. 相似文献
102.
Asuka Kamei Yuki Watanabe Fumika Shinozaki Akihito Yasuoka Takashi Kondo Tomoko Ishijima 《Bioscience, biotechnology, and biochemistry》2013,77(11):1893-1897
Effects of the administration of maple syrup extract (MSX) on hepatic gene expression were investigated in mice fed a high-fat diet. Gene annotation enrichment analysis based on gene ontology revealed some changes in the expression of genes related to lipid metabolism and the immune response in MSX-fed mice. Detailed analysis of these data indicated that MSX ingestion mitigates hepatic inflammation. 相似文献
103.
Nε-acetylation occurs on select lysine residues in α-crystallin of the human lens and alters its chaperone function. In this study, we investigated the effect of Nε-acetylation on advanced glycation end product (AGE) formation and consequences of the combined Nε-acetylation and AGE formation on the function of α-crystallin. Immunoprecipitation experiments revealed that Nε-acetylation of lysine residues and AGE formation co-occurs in both αA- and αB-crystallin of the human lens. Prior acetylation of αA- and αB-crystallin with acetic anhydride (Ac2O) before glycation with methylglyoxal (MGO) resulted in significant inhibition of the synthesis of two AGEs, hydroimidazolone (HI) and argpyrimidine. Similarly, synthesis of ascorbate-derived AGEs, pentosidine and Nε-carboxymethyl lysine (CML), was inhibited in both proteins by prior acetylation. In all cases, inhibition of AGE synthesis was positively related to the degree of acetylation. While prior acetylation further increased the chaperone activity of MGO-glycated αA-crystallin, it inhibited the loss of chaperone activity by ascorbate-glycation in both proteins. BioPORTER-mediated transfer of αA- and αB-crystallin into CHO cells resulted in significant protection against hyperthermia-induced apoptosis. This effect was enhanced in acetylated and MGO-modified αA- and αB-crystallin. Caspase-3 activity was reduced in α-crystallin transferred cells. Glycation of acetylated proteins with either MGO or ascorbate produced no significant change in the anti-apoptotic function. Collectively, these data demonstrate that lysine acetylation and AGE formation can occur concurrently in α-crystallin of human lens, and that lysine acetylation improves anti-apoptotic function of α-crystallin and prevents ascorbate-mediated loss of chaperone function. 相似文献
104.
Tomoko Igawa Yuki Yanagawa Shin-ya Miyagishima Toshiyuki Mori 《Journal of plant research》2013,126(3):387-394
Angiosperms have a unique sexual reproduction system called “double fertilization.” One sperm cell fertilizes the egg and another sperm cell fertilizes the central cell. To date, plant gamete membrane dynamics during fertilization has been poorly understood. To analyze this unrevealed gamete subcellular behavior, live cell imaging analyses of Arabidopsis double fertilization were performed. We produced female gamete membrane marker lines in which fluorescent proteins conjugated with PIP2a finely visualized egg cell and central cell surfaces. Using those lines together with a sperm cell membrane marker line expressing GCS1-GFP, the double fertilization process was observed. As a result, after gamete fusion, putative sperm plasma membrane GFP signals were occasionally detected on the egg cell surface adjacent to the central cell. In addition, time-lapse imaging revealed that GCS1-GFP signals entered both the egg cell and the central cell in parallel with the sperm cell movement toward the female gametes during double fertilization. These findings suggested that the gamete fusion process based on membrane dynamics was composed of (1) plasma membrane fusion on male and female gamete surfaces, (2) entry of sperm internal membrane components into the female gametes, and (3) plasmogamy. 相似文献
105.
Ki-Sung Kim Yuichiro Arima Taro Kitazawa Koichi Nishiyama Rieko Asai Yasunobu Uchijima Takahiro Sato Giovanni Levi Sachiko Kitanaka Takashi Igarashi Yukiko Kurihara Hiroki Kurihara 《Mechanisms of development》2013,130(11-12):553-566
Endothelin-1 (Edn1), originally identified as a vasoconstrictor peptide, is involved in the development of cranial/cardiac neural crest-derived tissues and organs. In craniofacial development, Edn1 binds to Endothelin type-A receptor (Ednra) to induce homeobox genes Dlx5/Dlx6 and determines the mandibular identity in the first pharyngeal arch. However, it remains unsolved whether this pathway is also critical for pharyngeal arch artery development to form thoracic arteries. Here, we show that the Edn1/Ednra signaling is involved in pharyngeal artery development by controlling the fate of neural crest cells through a Dlx5/Dlx6-independent mechanism. Edn1 and Ednra knock-out mice demonstrate abnormalities in pharyngeal arch artery patterning, which include persistent first and second pharyngeal arteries, resulting in additional branches from common carotid arteries. Neural crest cell labeling with Wnt1-Cre transgene and immunostaining for smooth muscle cell markers revealed that neural crest cells abnormally differentiate into smooth muscle cells at the first and second pharyngeal arteries of Ednra knock-out embryos. By contrast, Dlx5/Dlx6 knockout little affect the development of pharyngeal arch arteries and coronary arteries, the latter of which is also contributed by neural crest cells through an Edn-dependent mechanism. These findings indicate that the Edn1/Ednra signaling regulates neural crest differentiation to ensure the proper patterning of pharyngeal arch arteries, which is independent of the regional identification of the pharyngeal arches along the dorsoventral axis mediated by Dlx5/Dlx6. 相似文献
106.
Yasuhiro Ogawa Makoto Tanaka Miho Tanabe Toshihiro Suzuki Tadayasu Togawa Tomoko Fukushige Takuro Kanekura Hitoshi Sakuraba Kazuhiko Oishi 《PloS one》2013,8(1)
Sandhoff disease (SD) is a glycosphingolipid storage disease that arises from mutations in the Hexb gene and the resultant deficiency in β-hexosaminidase activity. This deficiency results in aberrant lysosomal accumulation of the ganglioside GM2 and related glycolipids, and progressive deterioration of the central nervous system. Dysfunctional glycolipid storage causes severe neurodegeneration through a poorly understood pathogenic mechanism. Induced pluripotent stem cell (iPSC) technology offers new opportunities for both elucidation of the pathogenesis of diseases and the development of stem cell-based therapies. Here, we report the generation of disease-specific iPSCs from a mouse model of SD. These mouse model-derived iPSCs (SD-iPSCs) exhibited pluripotent stem cell properties and significant accumulation of GM2 ganglioside. In lineage-directed differentiation studies using the stromal cell-derived inducing activity method, SD-iPSCs showed an impaired ability to differentiate into early stage neural precursors. Moreover, fewer neurons differentiated from neural precursors in SD-iPSCs than in the case of the wild type. Recovery of the Hexb gene in SD-iPSCs improved this impairment of neuronal differentiation. These results provide new insights as to understanding the complex pathogenic mechanisms of SD. 相似文献
107.
108.
Yuki Hatanaka Natsumi Shimizu Satoshi Nishikawa Mikiko Tokoro Seung-Wook Shin Takuji Nishihara Tomoko Amano Masayuki Anzai Hiromi Kato Tasuku Mitani Yoshihiko Hosoi Satoshi Kishigami Kazuya Matsumoto 《PloS one》2013,8(4)
After fertilization, the sperm and oocyte genomes undergo extensive epigenetic reprogramming to form a totipotent zygote. The dynamic epigenetic changes during early embryo development primarily involve DNA methylation and demethylation. We have previously identified Gse (gonad-specific expression gene) to be expressed specifically in germ cells and early embryos. Its encoded protein GSE is predominantly localized in the nuclei of cells from the zygote to blastocyst stages, suggesting possible roles in the epigenetic changes occurring during early embryo development. Here, we report the involvement of GSE in epigenetic reprogramming of the paternal genome during mouse zygote development. Preferential binding of GSE to the paternal chromatin was observed from pronuclear stage 2 (PN2) onward. A knockdown of GSE by antisense RNA in oocytes produced no apparent effect on the first and second cell cycles in preimplantation embryos, but caused a significant reduction in the loss of 5-methylcytosine (5mC) and the accumulation of 5-hydroxymethylcytosine (5hmC) in the paternal pronucleus. Furthermore, DNA methylation levels in CpG sites of LINE1 transposable elements, Lemd1, Nanog and the upstream regulatory region of the Oct4 (also known as Pou5f1) gene were clearly increased in GSE-knockdown zygotes at mid-pronuclear stages (PN3-4), but the imprinted H19-differential methylated region was not affected. Importantly, DNA immunoprecipitation of 5mC and 5hmC also indicates that knockdown of GSE in zygotes resulted in a significant reduction of the conversion of 5mC to 5hmC on LINE1. Therefore, our results suggest an important role of maternal GSE for mediating active DNA demethylation in the zygote. 相似文献
109.
To improve the pentose fermentation rate in Flammulina velutipes, the putative xylose isomerase (XI) gene from Arabidopsis thaliana was cloned and introduced into F. velutipes and the gene expression was evaluated in transformants. mRNA expression of the putative XI gene and XI activity were observed in two transformants, indicating that the putative gene from A. thaliana was successfully expressed in F. velutipes as a xylose isomerase. In addition, ethanol production from xylose was increased in the recombinant strains. This is the first report demonstrating the possibility of using plant genes as candidates for improving the characteristics of F. velutipes. 相似文献
110.
Keiko Sasaki Tomohiro Ichinose Tomoko Doko Ikuko Imoto Fred Jopp 《Landscape and Ecological Engineering》2016,12(1):61-72
Distributions of lucidophyllous species are limited due to the fragmentation of laurel forest. On Komayama Hill in central Japan, we evaluated the colonization of typical lucidophyllous vascular plants from a 350-year-old laurel forest into adjacent abandoned secondary forest for conservation and restoration purposes. A total of 14 consecutive subplots were established along the vegetation border between the two forests (length, 30 m; width, 5 m), extending 70 m into the secondary forest; 18 quadrats of old-growth forest were surveyed. Edge effects of old-growth forest were found to play an important role in re-establishing lucidophyllous saplings and seedlings in the secondary forest. In particular, the abundances of the four dominant canopy species of the old-growth forest significantly decreased with increasing distance. Hence, they are expected to colonize further into the secondary forest and, ultimately, to dominate the canopy. However, the number of lucidophyllous species did not change with distance. Species such as Ficus nipponica, Damnacanthus indicus, Ilex integra, and Lemmaphyllum microphyllum were near-completely or completely limited to the old-growth forest. They are known to be negatively affected by forest fragmentation and were observed to be struggling to colonize the exterior of the old-growth forest even after 60 years of abandonment. Their absence highlighted the limited colonization capacities of some old-growth forest species and underlined the time required for habitat restoration following human disturbance. We conclude that it is important to consider the population dynamics of dominant canopy species and the colonization of these interior species when assessing the habitat expansion of lucidophyllous species and hence the restoration of degraded lands. 相似文献