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101.
RhoD activated by fibroblast growth factor induces cytoneme-like cellular protrusions through mDia3C
Kazuhisa Koizumi Kazunori Takano Akiko Kaneyasu Haruko Watanabe-Takano Emi Tokuda Tomoyuki Abe Naoki Watanabe Tadaomi Takenawa Takeshi Endo 《Molecular biology of the cell》2012,23(23):4647-4661
The small GTPase RhoD regulates actin cytoskeleton to collapse actin stress fibers and focal adhesions, resulting in suppression of cell migration and cytokinesis. It also induces alignment of early endosomes along actin filaments and reduces their motility. We show here that a constitutively activated RhoD generated two types of actin-containing thin peripheral cellular protrusions distinct from Cdc42-induced filopodia. One was longer, almost straight, immotile, and sensitive to fixation, whereas the other was shorter, undulating, motile, and resistant to fixation. Moreover, cells expressing wild-type RhoD extended protrusions toward fibroblast growth factor (FGF) 2/4/8–coated beads. Stimulation of wild-type RhoD-expressing cells with these FGFs also caused formation of cellular protrusions. Nodules moved through the RhoD-induced longer protrusions, mainly toward the cell body. Exogenously expressed FGF receptor was associated with these moving nodules containing endosome-like vesicles. These results suggest that the protrusions are responsible for intercellular communication mediated by FGF and its receptor. Accordingly, the protrusions are morphologically and functionally equivalent to cytonemes. RhoD was activated by FGF2/4/8. Knockdown of RhoD interfered with FGF-induced protrusion formation. Activated RhoD specifically bound to mDia3C and facilitated actin polymerization together with mDia3C. mDia3C was localized to the tips or stems of the protrusions. In addition, constitutively activated mDia3C formed protrusions without RhoD or FGF stimulation. Knockdown of mDia3 obstructed RhoD-induced protrusion formation. These results imply that RhoD activated by FGF signaling forms cytoneme-like protrusions through activation of mDia3C, which induces actin filament formation. 相似文献
102.
103.
Shimamoto S Takata M Tokuda M Oohira F Tokumitsu H Kobayashi R 《The Journal of biological chemistry》2008,283(42):28246-28258
S100A2 and S100A6 interact with several target proteins in a Ca2+-regulated manner. However, the exact intracellular roles of the S100 proteins are unclear. In this study we identified Hsp70/Hsp90-organizing protein (Hop) and kinesin light chain (KLC) as novel targets of S100A2 and S100A6. Hop directly associates with Hsp70 and Hsp90 through the tetratricopeptide (TPR) domains and regulates Hop-Hsp70 and Hop-Hsp90 complex formation. We have found that S100A2 and S100A6 bind to the TPR domain of Hop, resulting in inhibition of the Hop-Hsp70 and Hop-Hsp90 interactions in vitro. Although endogenous Hsp70 and Hsp90 interact with Hop in resting Cos-7 cells, but not with S100A6, stimulation of these cells with ionomycin caused a Hop-S100A6 interaction, resulting in the dissociation of Hsp70 and Hsp90 from Hop. Similarly, glutathione S-transferase pulldown and co-immunoprecipitation experiments revealed that S100A6 binds to the TPR domain of KLC, resulting in inhibition of the KLC-c-Jun N-terminal kinase (JNK)-interacting protein 1 (JIP-1) interaction in vitro. The transiently expressed JIP-1 interacts with KLC in resting Cos-7 cells but not with S100A6. Stimulation of these cells with ionomycin also caused a KLC-S100A6 interaction, resulting in dissociation of JIP-1 from KLC. These results strongly suggest that the S100 proteins modulate Hsp70-Hop-Hsp90 multichaperone complex formation and KLC-cargo interaction via Ca2+-dependent S100 protein-TPR protein complex formation in vivo as well as in vitro. Moreover, we have shown that S100A2 and S100A6 interact with another TPR protein Tom70 and regulate the Tom70-ligand interaction in vitro. Thus, our findings suggest a new intracellular Ca2+-signaling pathway via S100 proteins-TPR motif interactions. 相似文献
104.
Kawashima Y Miyazaki E Müller M Tokuda H Nishiyama K 《The Journal of biological chemistry》2008,283(36):24489-24496
We recently found that the spontaneous integration of M13 procoat is blocked by diacylglycerol (DAG) (Nishiyama, K., Ikegami, A., Moser, M., Schiltz, E., Tokuda, H., and Muller, M. (2006) J. Biol. Chem. 281, 35667-35676). Here, we demonstrate that the spontaneous integration of Pf3 coat, another membrane protein that has been thought to be integrated spontaneously into liposomes, can be blocked by DAG at physiological concentrations. Moreover, the spontaneous integration of the membrane potential-independent version of Pf3 coat (3L-Pf3 coat), which is independent of YidC, was also blocked by DAG. To clarify the mechanism by which DAG blocks spontaneous integration, we examined lipid compounds similar to DAG and DAG derivatives. The blockage of spontaneous integration was specific to DAG, as fatty acids, monoacylglycerol, and phosphatidic acids were not effective for the blockage. When the acyl chains in DAG were shortened even to octanoyl residues, it still blocked spontaneous integration, whereas diheptanoylglycerol did not block it at all. Triacylglycerol was more effective than DAG. However, the lipid A-derivative-dependent integration of M13 procoat could not be reconstituted when triacylglycerol was included in the liposomes. On the other hand, when DAG was included in the liposomes, we found that the integration of 3L-Pf3 coat was strictly dependent on the lipid A-derived integration factor. We propose that the bulky structure of DAG rather than changes in membrane curvature is essential for the blockage of spontaneous integration. We also demonstrated that the blockage of spontaneous integration by DAG is also operative in native membrane vesicles. 相似文献
105.
An ATP binding cassette transporter LolCDE complex releases lipoproteins from the inner membrane of Escherichia coli in an ATP-dependent manner, leading to the formation of a complex between a lipoprotein and a periplasmic chaperone, LolA. LolA is proposed to undergo a conformational change upon the lipoprotein binding. The lipoprotein is then transferred from the LolA-lipoprotein complex to the outer membrane via LolB. Unlike most ATP binding cassette transporters mediating the transmembrane flux of substrates, the LolCDE complex catalyzes the extrusion of lipoproteins anchored to the outer leaflet of the inner membrane. Moreover, the LolCDE complex is unique in that it can be purified as a liganded form, which is an intermediate of the lipoprotein release reaction. Taking advantage of these unique properties, we established an assay system that enabled the analysis of a single cycle of lipoprotein transfer reaction from liganded LolCDE to LolA in a detergent solution. The LolA-lipoprotein complex thus formed was physiologically functional and delivered lipoproteins to the outer membrane in a LolB-dependent manner. Vanadate, a potent inhibitor of the lipoprotein release from proteoliposomes, was found to inhibit the release of ADP from LolCDE. However, a single cycle of lipoprotein transfer occurred from vanadate-treated LolCDE to LolA, indicating that vanadate traps LolCDE at the energized state. 相似文献
106.
Suzuki S Uchida D Koide H Suyama K Shibata T Yoshida T Tanaka T Noguchi Y Saito Y Tatsuno I 《Peptides》2008,29(12):2225-2231
Vasopressin was reported to stimulate secretion of both cortisol and aldosterone through eutopic V1a receptors in adrenal gland. Recently, adrenal hyper-responsiveness of plasma cortisol to vasopressin with eutopic overexpession of V1a receptors has been reported in Cushing's syndrome, such as a majority of cases of ACTH-independent macronodular adrenal hyperplasia and some cases of Cushing's adenomas. There were a few reports regarding the aldosterone response to vasopressin in aldosterone-producing adenoma. The aim of our study was to investigate the aldosterone response to vasopressin and its pathophysiological roles in the patients with aldosterone-producing adenoma. Vasopressin-loading test was performed in 10 patients with aldosterone-producing adenoma, and in 16 patients with non-functioning adrenal tumors. The roles of the aldosterone response to vasopressin were analyzed in terms of hormonal secretion and the expression of V1a receptor mRNA on the operated adrenal gland in aldosterone-producing adenoma. We found that (1) a varying aldosterone response to vasopressin was observed, (2) absolute response of plasma aldosterone in aldosterone-producing adenoma was significantly higher than that in non-functioning tumor, (3) aldosterone response rate to vasopressin was significantly and negatively correlated with the decline rate (%) in plasma aldosterone from morning to evening in aldosterone-producing adenoma, (4) V1a receptor mRNA was expressed at various values in aldosterone-producing adenoma, and (5) surgical removal of aldosterone-producing adenoma eliminated the aldosterone response to vasopressin observed in patients with aldosterone-producing adenoma. These findings indicated that vasopressin might be involved in the coordination of aldosterone secretion through eutopic expression of V1a receptor in aldosterone-producing adenoma. 相似文献
107.
The structures of a lipoprotein carrier, LolA, and a lipoprotein receptor, LolB, are similar except for an extra C-terminal loop containing a 3(10) helix and beta-strand 12 in LolA. Lipoprotein release was significantly reduced when beta-12 was deleted. Deletion of the 3(10) helix also inhibited the lipoprotein release. Furthermore, lipoproteins were non-specifically localized to membranes when LolA lacked the 3(10) helix. Thus, the membrane localization of lipoproteins with the LolA derivative lacking the 3(10) helix was independent of LolB whereas LolB was essential for the outer membrane localization of lipoproteins with the wild-type LolA. 相似文献
108.
Miyanishi N Sato N Nakakita S Sumiyoshi W Morimoto K Okuma H Tokuda M Izumori K Watanabe E Hirabayashi J 《Biosensors & bioelectronics》2008,23(9):1347-1352
The aim of this study was to develop a simple, rapid and highly sensitive sensor for measuring the rare sugar d-psicose. The proposed system adopts amperometric flow analysis and two consecutive enzyme reactions consisting of a reactor packed with d-tagatose 3-epimerase (DTE)-immobilized beads, which converts d-psicose to d-fructose, and a carbon-paste electrode containing d-fructose dehydrogenase (DFDH). In order to fabricate a robust sensor system, various experimental parameters were optimized including the buffer composition, flow rate for the two enzyme reactions and the size of micro-flow cell. The developed sensor responded linearly to d-psicose concentration in the range from 0.08 to 50mM (R(2)=0.988). The signal/noise ratio was 3.0 for the 0.08 mM d-psicose solution, and the relative standard deviations were 1.7 (n=20) and 2.6% (n=20) for the 10 and 20mM d-psicose solutions, respectively. One round of assay was completed within 8 min. Our results suggest that the sensor can be used not only for the detection of d-psicose in food samples but also for monitoring d-psicose within the environment. Moreover, the sensor system can be applied to the detection of many other rare sugars by using the same measurement principle. 相似文献
109.
We conducted a 3-year study of a natural population of the willow leaf beetle Plagiodera versicolora (Coleoptera: Chrysomelidae) on a river bank of the Inukami River, Shiga, central Japan, where four willow species (Salix chaenomeloides, S. eriocarpa, S. integra, and S. serissaefolia) occur sympatrically. Our survey showed that: (1) at the study site, the abundance of P. versicolora greatly varied among years and among willow species; (2) adult abundance changed seasonally with species-specific patterns on different willow species; and (3) the dispersal-settlement of adults had the most pronounced effects on the seasonal population growth rate of P. versicolora. Factors affecting these results were discussed. 相似文献
110.
Tokuda S Niisato N Nakajima K Marunaka Y 《Biochemical and biophysical research communications》2008,366(2):464-470
In the present study, we investigated the effect of osmolality on the paracellular ion conductance (Gp) composed of the Na+ conductance (GNa) and the Cl− conductance (GCl). An osmotic gradient generated by NaCl with relatively apical hypertonicity (NaCl-absorption-direction) induced a large increase in the GNa associated with a small increase in the GCl, whereas an osmotic gradient generated by NaCl with relatively basolateral hypertonicity (NaCl-secretion-direction) induced small increases in the GNa and the GCl. These increases in the Gp caused by NaCl-generated osmotic gradients were diminished by the application of sucrose canceling the NaCl-generated osmotic gradient. The osmotic gradient generated by basolateral application of sucrose without any NaCl gradients had little effects on the Gp. However, this basolateral application of sucrose produced a precondition drastically quickening the time course of the action of the NaCl-generated osmotic gradient on the Gp. Further, we found that application of the basolateral hypotonicity generated by reduction of NaCl concentration shifted the localization of claudin-1 to the apical from the basolateral side. These results indicate that the osmotic gradient regulates the paracellular ion conductive pathway of tight junctions via a mechanism dependent on the direction of NaCl gradients associated with a shift of claudin-1 localization to the apical side in renal A6 epithelial cells. 相似文献