全文获取类型
收费全文 | 3544篇 |
免费 | 187篇 |
国内免费 | 2篇 |
出版年
2022年 | 19篇 |
2021年 | 44篇 |
2020年 | 22篇 |
2019年 | 43篇 |
2018年 | 42篇 |
2017年 | 50篇 |
2016年 | 73篇 |
2015年 | 120篇 |
2014年 | 126篇 |
2013年 | 209篇 |
2012年 | 228篇 |
2011年 | 219篇 |
2010年 | 148篇 |
2009年 | 159篇 |
2008年 | 205篇 |
2007年 | 209篇 |
2006年 | 198篇 |
2005年 | 198篇 |
2004年 | 179篇 |
2003年 | 176篇 |
2002年 | 180篇 |
2001年 | 48篇 |
2000年 | 38篇 |
1999年 | 59篇 |
1998年 | 35篇 |
1997年 | 38篇 |
1996年 | 32篇 |
1995年 | 23篇 |
1994年 | 17篇 |
1993年 | 35篇 |
1992年 | 50篇 |
1991年 | 56篇 |
1990年 | 46篇 |
1989年 | 60篇 |
1988年 | 39篇 |
1987年 | 25篇 |
1986年 | 30篇 |
1985年 | 25篇 |
1984年 | 26篇 |
1983年 | 26篇 |
1982年 | 29篇 |
1981年 | 16篇 |
1980年 | 12篇 |
1979年 | 13篇 |
1978年 | 11篇 |
1975年 | 9篇 |
1974年 | 18篇 |
1973年 | 7篇 |
1972年 | 9篇 |
1970年 | 7篇 |
排序方式: 共有3733条查询结果,搜索用时 15 毫秒
991.
Hirata D Kishimoto N Suda M Sogabe Y Nakagawa S Yoshida Y Sakai K Mizunuma M Miyakawa T Ishiguro J Toda T 《The EMBO journal》2002,21(18):4863-4874
Fission yeast cells identify growing regions at the opposite ends of the cell, producing the rod-like shape. The positioning of the growth zone(s) and the polarized growth require CLIP170-like protein Tip1 and the Ndr kinase Orb6, respectively. Here, we show that the mor2/cps12 mutation disrupts the localization of F-actin at the cell ends, producing spherical cells and concomitantly inducing a G(2) delay at 36 degrees C. Mor2 is important for the localization of F-actin at the cell end(s) but not at the medial region, and is essential for the restriction of the growth zone(s) where Tip1 targets. Mor2 is homologous to the Drosophila Furry protein, which is required to maintain the integrity of cellular extensions, and is localized at both cell ends and the medial region of the cell in an actin-dependent fashion. Cellular localization of Mor2 and Orb6 was interdependent. The tyrosine kinase Wee1 is necessary for the G(2) delay and maintenance of viability of the mor2 mutant. These results indicate that Mor2 plays an essential role in cell morphogenesis in concert with Orb6, and the mutation activates the mechanism coordinating morphogenesis with cell cycle progression. 相似文献
992.
993.
Role of PTB-like protein,a neuronal RNA-binding protein,during the differentiation of PC12 cells 总被引:2,自引:0,他引:2
Ichikawa M Kikuchi T Tateiwa H Gotoh N Ohta K Arai J Yoshimura N 《Journal of biochemistry》2002,131(6):861-868
PTB-like protein (PTBLP) is a new homologue of pyrimidine tract binding protein (PTB), and has been cloned as a possible autoantigen in cancer-associated retinopathy. PTBLP has two functional domains, the nuclear localization signal and the RNA recognition motifs (RRMs). Full-length PTBLP (PTBLP-L) has four RRMs, and its alternative splicing product (PTBLP-S) lacks the third and fourth RRMs. Although PTBLPs are expressed in neuronal tissues, the function of PTBLPs has not been determined. We have studed whether PTBLP plays a role in neuronal differentiation using PC12 cells. During the process of nerve growth factor-induced neuronal differentiation of PC12 cells, PTBLP-L was down-regulated whereas PTBLP-S was up-regulated. Transfection of PTBLP-L into PC12 cells led to the suppression of neuronal differentiation. In PTBLP-S transfected cells, however, this suppression was not evident. When both PTBLP-L and PTBLP-S were co-transfected, the suppressive effect of PTBLP-L decreased. In differentiated cells, PTBLP-S localized in the nucleus and PTBLP-L was found dispersed throughout the cytoplasm and neuronal growth cone. These findings suggest that PTBLP-L acts as a negative regulator of neuronal differentiation and PTBLP-S acts as a competitor of PTBLP-L. 相似文献
994.
Lee JR Takenaka H Takahashi N Makise M Yamaguchi Y Tsuchiya T Mizushima T 《Journal of biochemistry》2002,131(4):541-546
Origin Recognition Complex (ORC) is a candidate initiator of chromosomal DNA replication in eukaryotes. We recently reported that cardiolipin inhibits the interaction of Origin Recognition Complex ORC with origin DNA, as is the case of DnaA, the initiator of chromosomal DNA replication in prokaryotes. We report here that another acidic phospholipid, phosphatidylglycerol (PG), also inhibits the interaction. Synthetic PG with only unsaturated fatty acids inhibits ORC-binding to origin DNA more strongly than PG with only saturated fatty acids. On the other hand, phosphatidylcholine (neutral phospholipid) does not affect the ORC-origin interaction, regardless of the presence of saturated or unsaturated fatty acids. These results suggest that an acidic moiety and unsaturated fatty acids are important factors for the inhibitory effect of phospholipids on ORC binding to origin DNA, as is the case for DnaA. The inhibitory effect of cardiolipin on ORC binding to origin DNA was more apparent at 30 degrees C than at 4 degrees C. Furthermore, chlorpromazine restored the ORC-origin interaction in the presence of cardiolipin. Since the presence of unsaturated fatty acids, low incubation temperatures, and the addition of chlorpromazine all decrease membrane fluidity, these results suggest that membrane fluidity is important for the inhibitory effect of acidic phospholipids on ORC-binding to origin DNA, as is the case for DnaA. 相似文献
995.
Morisaki T Hirota T Iida S Marumoto T Hara T Nishiyama Y Kawasuzi M Hiraoka T Mimori T Araki N Izawa I Inagaki M Saya H 《FEBS letters》2002,529(2-3):319-324
Identification of physiological substrates for Cdc2/cyclin B is crucial for understanding the functional link between mitotic events and Cdc2/cyclin B activation. A human homologue of the Drosophila warts tumor suppressor, termed WARTS, is a serine/threonine kinase and a dynamic component of the mitotic apparatus. We have found that Cdc2/cyclin B forms a complex with a fraction of WARTS in the centrosome and phosphorylates the Ser613 site of WARTS during mitosis. Immunocytochemical analysis has shown that the S613-phosphorylated WARTS appears in the spindle poles at prometaphase and disappears at telophase. Our findings suggest that Cdc/cyclin B regulates functions of WARTS on the mitotic apparatus. 相似文献
996.
997.
Rac1 and Cdc42 capture microtubules through IQGAP1 and CLIP-170 总被引:27,自引:0,他引:27
Fukata M Watanabe T Noritake J Nakagawa M Yamaga M Kuroda S Matsuura Y Iwamatsu A Perez F Kaibuchi K 《Cell》2002,109(7):873-885
Linkage of microtubules to special cortical regions is essential for cell polarization. CLIP-170 binds to the growing ends of microtubules and plays pivotal roles in orientation. We have found that IQGAP1, an effector of Rac1 and Cdc42, interacts with CLIP-170. In Vero fibroblasts, IQGAP1 localizes at the polarized leading edge. Expression of carboxy-terminal fragment of IQGAP1, which includes the CLIP-170 binding region, delocalizes GFP-CLIP-170 from the tips of microtubules and alters the microtubule array. Activated Rac1/Cdc42, IQGAP1, and CLIP-170 form a tripartite complex. Furthermore, expression of an IQGAP1 mutant defective in Rac1/Cdc42 binding induces multiple leading edges. These results indicate that Rac1/Cdc42 marks special cortical spots where the IQGAP1 and CLIP-170 complex is targeted, leading to a polarized microtubule array and cell polarization. 相似文献
998.
The complete nucleotide sequence of the mitochondrial genome was determined for a harpacticoid copepod, Tigriopus japonicus
(Crustacea), using an approach that employs a long polymerase chain reaction technique and primer walking. Although the genome
(14,628 bp) contained the same set of 37 genes (2 ribosomal RNA, 22 transfer RNA, and 13 protein-coding genes) as found in
other metazoan animals, none of the previously reported gene orders were comparable to that of T. japonicus. Furthermore,
all genes were encoded on one strand, unlike the mitochondrial genomes of most metazoan animals. Size reductions were notable
for tRNA and rRNA genes, resulting in one of the smallest mitochondrial genomes in the arthropod lineage. Although it appears
that such large-scale gene rearrangements have occurred in the ancestral species of T. japonicus, none of the proposed mechanisms
parsimoniously account for this eccentric gene arrangement. 相似文献
999.
Kamenosono T Shimada H Funakoshi T Kojima S Imamura Y 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2002,132(1):61-66
The structural characteristics of several dithiocarbamates (DTCs) [N-p-methylbenzyl-D-glucamine dithiocarbamate (MBGD), N-benzyl-D-glucamine dithiocarbamate (BGD), N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD) and N-p-carboxybenzyl-D-glucamine dithiocarbamate (CBGD)] that induce in vivo mobilization of cadmium (Cd) were examined in mice. The renal and hepatic contents of Cd were lower in the treatments with Cd-DTC combinations than in that with Cd alone. Probenecid pretreatment decreased the renal content of Cd in Cd-MBGD and Cd-BGD treated mice, but it increased the renal content of Cd and decreased the urinary excretion of the metal in Cd-HBGD and Cd-CBGD treated mice. Furthermore, although ureter-ligation did not affect the renal content of Cd in Cd-MBGD and Cd-BGD treated mice, it increased the renal content of Cd in Cd-HBGD and Cd-CBGD treated mice. These findings suggest that Cd-MBGD and Cd-BGD complexes are taken up into the tubular cells by an organic anion transport system through the basolateral membrane, whereas Cd-HBGD and Cd-CBGD complexes are secreted to the tubular lumen by an organic anion transport system through the brush border membrane. The results of probenecid pretreatment also led us to assume that the hepatic transport of these four Cd-DTC complexes is regulated, at least in part, by a probenecid-sensitive organic anion transport system. 相似文献
1000.
Yoshihiro Yasui Mutsuki Amano Koh-ichi Nagata Naoyuki Inagaki Hideo Nakamura Hideyuki Saya Kozo Kaibuchi Masaki Inagaki 《The Journal of cell biology》1998,143(5):1249-1258
Rho-associated kinase (Rho-kinase), which is activated by the small GTPase Rho, regulates formation of stress fibers and focal adhesions, myosin fiber organization, and neurite retraction through the phosphorylation of cytoskeletal proteins, including myosin light chain, the ERM family proteins (ezrin, radixin, and moesin) and adducin. Rho-kinase was found to phosphorylate a type III intermediate filament (IF) protein, glial fibrillary acidic protein (GFAP), exclusively at the cleavage furrow during cytokinesis. In the present study, we examined the roles of Rho-kinase in cytokinesis, in particular organization of glial filaments during cytokinesis. Expression of the dominant-negative form of Rho-kinase inhibited the cytokinesis of Xenopus embryo and mammalian cells, the result being production of multinuclei. We then constructed a series of mutant GFAPs, where Rho-kinase phosphorylation sites were variously mutated, and expressed them in type III IF-negative cells. The mutations induced impaired segregation of glial filament (GFAP filament) into postmitotic daughter cells. As a result, an unusually long bridge-like cytoplasmic structure formed between the unseparated daughter cells. Alteration of other sites, including the cdc2 kinase phosphorylation site, led to no remarkable defect in glial filament separation. These results suggest that Rho-kinase is essential not only for actomyosin regulation but also for segregation of glial filaments into daughter cells which in turn ensures correct cytokinetic processes. 相似文献