全文获取类型
收费全文 | 540篇 |
免费 | 34篇 |
国内免费 | 2篇 |
出版年
2022年 | 2篇 |
2021年 | 6篇 |
2020年 | 3篇 |
2019年 | 6篇 |
2018年 | 6篇 |
2017年 | 6篇 |
2016年 | 15篇 |
2015年 | 23篇 |
2014年 | 22篇 |
2013年 | 35篇 |
2012年 | 27篇 |
2011年 | 38篇 |
2010年 | 18篇 |
2009年 | 18篇 |
2008年 | 29篇 |
2007年 | 30篇 |
2006年 | 37篇 |
2005年 | 30篇 |
2004年 | 35篇 |
2003年 | 27篇 |
2002年 | 21篇 |
2001年 | 14篇 |
2000年 | 8篇 |
1999年 | 8篇 |
1998年 | 6篇 |
1997年 | 3篇 |
1996年 | 3篇 |
1995年 | 7篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 4篇 |
1990年 | 9篇 |
1989年 | 8篇 |
1988年 | 9篇 |
1987年 | 3篇 |
1986年 | 5篇 |
1985年 | 5篇 |
1984年 | 7篇 |
1983年 | 5篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1980年 | 3篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1971年 | 1篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1958年 | 2篇 |
1956年 | 1篇 |
排序方式: 共有576条查询结果,搜索用时 937 毫秒
51.
Kaseda R Iino N Hosojima M Takeda T Hosaka K Kobayashi A Yamamoto K Suzuki A Kasai A Suzuki Y Gejyo F Saito A 《Biochemical and biophysical research communications》2007,357(4):1130-1134
Serum levels of cystatin C, an endogenous cysteine proteinase inhibitor, are often used as an indicator of glomerular filtration rate. Although it is known that cystatin C is filtered by glomeruli and metabolized in proximal tubule cells (PTC), the precise molecular mechanism underlying this process is undetermined. Using quartz-crystal microbalance analyses, we demonstrate that cystatin C binds directly to megalin, an endocytic receptor in PTC, in a Ca(+)-dependent manner. We also find that cystatin C is endocytosed specifically via megalin in rat yolk sac epithelium-derived L2 cells which share a variety of characteristics with PTC. Finally, in vivo studies using kidney-specific megalin knockout mice provide evidence that megalin mediates proximal tubular uptake of cystatin C. We conclude that megalin is an endocytic receptor of cystatin C in PTC. 相似文献
52.
Ha Lee J Hee Lee I Noda H Mita K Taniai K 《Insect biochemistry and molecular biology》2007,37(12):1338-1347
We verified the efficacy of lipopolysaccharide (LPS) in activating the cecropin B gene (CecB) in an immune-competent Bombyx mori cell line. Strong activation of CecB by the LPSs from Escherichia coli, Pseudomonas aeruginosa, and Salmonella minnesota were completely eliminated after digestion of the LPSs with muramidase. The results clearly indicate that a polymer form of PGN in the LPSs elicited CecB. An oligonucleotide microarray screen revealed that none of the 16,000 genes on the array were activated by LPS in the cells. In contrast, E. coli PGN strongly elicited five antibacterial peptide genes and numerous other genes, and PGN from Micrococcus luteus activated only several genes. Semi-quantitative RT-PCR revealed that all antibacterial genes activated by both PGNs, but the extents were 10–100 times higher with E. coli PGN. Similarly, higher elicitor activity of E. coli than M. luteus was indicated using peptidoglycan recognition protein gene, which is involved in pro-phenol oxidase cascade. 相似文献
53.
Takeshi Inagaki Satoshi Iwasaki Yoshihiro Matsumura Takeshi Kawamura Toshiya Tanaka Yohei Abe Ayumu Yamasaki Yuya Tsurutani Ayano Yoshida Yoko Chikaoka Kanako Nakamura Kenta Magoori Ryo Nakaki Timothy F. Osborne Kiyoko Fukami Hiroyuki Aburatani Tatsuhiko Kodama Juro Sakai 《The Journal of biological chemistry》2015,290(7):4163-4177
Polycomb repressive complex 1 (PRC1) plays an essential role in the epigenetic repression of gene expression during development and cellular differentiation via multiple effector mechanisms, including ubiquitination of H2A and chromatin compaction. However, whether it regulates the stepwise progression of adipogenesis is unknown. Here, we show that FBXL10/KDM2B is an anti-adipogenic factor that is up-regulated during the early phase of 3T3-L1 preadipocyte differentiation and in adipose tissue in a diet-induced model of obesity. Interestingly, inhibition of adipogenesis does not require the JmjC demethylase domain of FBXL10, but it does require the F-box and leucine-rich repeat domains, which we show recruit a noncanonical polycomb repressive complex 1 (PRC1) containing RING1B, SKP1, PCGF1, and BCOR. Knockdown of either RING1B or SKP1 prevented FBXL10-mediated repression of 3T3-L1 preadipocyte differentiation indicating that PRC1 formation mediates the inhibitory effect of FBXL10 on adipogenesis. Using ChIP-seq, we show that FBXL10 recruits RING1B to key specific genomic loci surrounding the key cell cycle and the adipogenic genes Cdk1, Uhrf1, Pparg1, and Pparg2 to repress adipogenesis. These results suggest that FBXL10 represses adipogenesis by targeting a noncanonical PRC1 complex to repress key genes (e.g. Pparg) that control conversion of pluripotent cells into the adipogenic lineage. 相似文献
54.
Life history strategy and adult and larval behavior of Macrodiplosis selenis (Diptera: Cecidomyiidae), a species that induces leaf‐margin fold galls on deciduous Quercus (Fagaceae) 下载免费PDF全文
Wanggyu Kim Kiyoko Matsunaga Naohisa Gyoutoku Kazunori Matsuo Tsuneo Minami Junichi Yukawa 《Entomological Science》2015,18(4):470-478
Life historical, behavioral and ecological traits of Macrodiplosis selenis, which induces leaf‐margin fold galls on Quercus serrata, Q. mongolica and Q. dentata (Fagaceae) in Japan and South Korea, were studied. Daily activity and larval development indicate that M. selenis is a diurnal and univoltine gall midge. In April, females lay their eggs both on upper and under surfaces of fresh leaves. The duration of the egg stage varies from 5 to 9 days, depending on daily temperatures. Hatched larvae crawl to the upper surface of the leaf margin, where they start to induce galls. Larvae become full‐grown in October, drop to the ground in November and overwinter in cocoons on the ground, while larvae of congeners mature in May and drop to the ground in June. A relatively long period of the second larval stadium from July to October on the host trees seems to be effective for M. selenis in avoiding summer mortalities caused by predation and aridity on the ground and by ectoparasitoids that attack mature larvae or pupae on the host leaves. The spatial distribution pattern of M. selenis leaf galls is contagious and the mean gall density per leaf is significantly correlated with the mean crowding. This study adds new insights of life history strategy and adult and larval behavioral pattern to the ecological knowledge of gall midges, and these kinds of information are essential for further studies of M. selenis population dynamics and interactions with other Quercus‐associated herbivores. 相似文献
55.
Kiyoko Yokota Robert W. Sterner 《Proceedings. Biological sciences / The Royal Society》2011,278(1704):458-463
Multicellular organisms that benefit from division of labour are presumably descended from colonial species that initially derived benefits from larger colony size, before the evolution of specialization. Life in a colony can have costs as well as benefits, but these can be hard to measure. We measured physiological costs to life in a colony using a novel method based on population dynamics, comparing growth rates of unicells and kairomone-induced colonies of a green alga Desmodesmus subspicatus against a reference co-occurring species. Coloniality negatively affected growth during the initial log growth phase, while no adverse effect was detected under nutrient-limited competitive conditions. The results point to costs associated with traits involved in rapid growth rather than those associated with efficient growth under resource scarcity. Some benefits of coloniality (e.g. defence from herbivory) may be different from when this trait evolved, but our approach shows how costs would have depended on conditions. 相似文献
56.
Yamada Y Yamada K Nomura N Yamano A Kimura R Naiki M Fukushi D Wakamatsu N Taniguchi A Yamaoka N Kaneko K Fujimori S 《Nucleosides, nucleotides & nucleic acids》2011,30(12):1272-1275
Mutations of two enzyme genes, HPRT1 encoding hypoxanthine guanine phosphoribosyltransferase (HPRT) and PRPS1 encoding a catalytic subunit (PRS-I) of phosphoribosylpyrophosphate synthetase, cause X-linked inborn errors of purine metabolism. Analyzing these two genes, we have identified three HPRT1 mutations in Lesch-Nyhan families following our last report. One of them, a new mutation involving the deletion of 4224 bp from intron 4 to intron 5 and the insertion of an unknown 28 bp, has been identified. This mutation resulted in an enzyme polypeptide with six amino acids deleted due to abnormal mRNA skipping exon 5. The other HPRT1 mutations, a single base deletion (548delT, 183fs189X), and a point mutation causing a splicing error (532+1G>A, 163fs165X) were detected first in Japanese patients but have been reported in European families. On the other hand, in the analysis of PRPS1, no mutation was identified in any patient. 相似文献
57.
Sato K Watanabe T Wang S Kakeno M Matsuzawa K Matsui T Yokoi K Murase K Sugiyama I Ozawa M Kaibuchi K 《Molecular biology of the cell》2011,22(17):3103-3119
Cadherin trafficking controls tissue morphogenesis and cell polarity. The endocytic adaptor Numb participates in apicobasal polarity by acting on intercellular adhesions in epithelial cells. However, it remains largely unknown how Numb controls cadherin-based adhesion. Here, we found that Numb directly interacted with p120 catenin (p120), which is known to interact with E-cadherin and prevent its internalization. Numb accumulated at intercellular adhesion sites and the apical membrane in epithelial cells. Depletion of Numb impaired E-cadherin internalization, whereas depletion of p120 accelerated internalization. Expression of the Numb-binding fragment of p120 inhibited E-cadherin internalization in a dominant-negative fashion, indicating that Numb interacts with the E-cadherin/p120 complex and promotes E-cadherin endocytosis. Impairment of Numb induced mislocalization of E-cadherin from the lateral membrane to the apical membrane. Atypical protein kinase C (aPKC), a member of the PAR complex, phosphorylated Numb and inhibited its association with p120 and α-adaptin. Depletion or inhibition of aPKC accelerated E-cadherin internalization. Wild-type Numb restored E-cadherin internalization in the Numb-depleted cells, whereas a phosphomimetic mutant or a mutant with defective α-adaptin-binding ability did not restore the internalization. Thus, we propose that aPKC phosphorylates Numb to prevent its binding to p120 and α-adaptin, thereby attenuating E-cadherin endocytosis to maintain apicobasal polarity. 相似文献
58.
Goro Yoshizaki Kiyoko Fujinuma Yoshiko Iwasaki Tomoyuki Okutsu Shinya Shikina Ryosuke Yazawa Yutaka Takeuchi 《Comparative biochemistry and physiology. Part D, Genomics & proteomics》2011,6(1):55-61
Recent progress in genome-based breeding has created various fish strains carrying desirable genetic traits; however, methods for the long-term preservation of their genetic resources have not yet been developed, mainly due to the lack of cryopreservation techniques for fish eggs and embryos. Recently, we established an alternative cryopreservation technique for fish spermatogonia using a slow-freezing method. Furthermore, we developed a transplantation system to produce functional eggs and sperm derived from spermatogonia. Spermatogonia isolated from the testes of vasa-green fluorescent protein (Gfp) transgenic rainbow trout (Oncorhynchus mykiss) were transplanted into the peritoneal cavity of triploid masu salmon (Oncorhynchus masou) hatchlings of both genders. The transplanted trout spermatogonia migrated towards the gonadal anlagen of the recipient salmon, into which they were subsequently incorporated. We confirmed that the donor-derived spermatogonia resumed gametogenesis, and produced sperm and eggs in male and female recipient salmon, respectively. Fertilization of the resultant eggs and sperm produced only rainbow trout in the first filial (F1) generation, suggesting that the sterile triploid recipient salmon produced functional eggs and sperm derived from the trout donors. A combination of spermatogonial transplantation and cryopreservation could be a powerful tool for preserving valuable fish strains with desirable genetic traits and endangered species. 相似文献
59.
Phospholipase C-delta1 and -delta3 are essential in the trophoblast for placental development 下载免费PDF全文
Nakamura Y Hamada Y Fujiwara T Enomoto H Hiroe T Tanaka S Nose M Nakahara M Yoshida N Takenawa T Fukami K 《Molecular and cellular biology》2005,25(24):10979-10988
Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in phosphoinositide turnover and is involved in a variety of physiological functions. We analyzed PLCdelta1 knockout mice and found that PLCdelta1 is required for the maintenance of skin homeostasis. However, there were no remarkable abnormalities except hair loss and runting in PLCdelta1 knockout mice, even though PLCdelta1 is broadly distributed. Here, we report that mice lacking both PLCdelta1 and PLCdelta3 died at embryonic day 11.5 (E11.5) to E13.5. PLCdelta1/PLCdelta3 double-knockout mice exhibited severe disruption of the normal labyrinth architecture in the placenta and decreased placental vascularization, as well as abnormal proliferation and apoptosis of trophoblasts in the labyrinth area. Furthermore, PLCdelta1/PLCdelta3 double-knockout embryos supplied with a normal placenta by the tetraploid aggregation method survived beyond E14.5, clearly indicating that the embryonic lethality is caused by a defect in trophoblasts. On the basis of these results, we conclude that PLCdelta1 and PLCdelta3 are essential in trophoblasts for placental development. 相似文献
60.