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51.
52.
Akihisa Takahashi Naoaki Shibata Shoko Nishikawa Ken Ohnishi Noriaki Ishioka Takeo Ohnishi 《Photochemical & photobiological sciences》2006,5(5):467-471
Phytoplankton such as Euglena are constantly exposed to solar light which is used for photosynthesis. Although the solar ultraviolet (UV) induces DNA damage such as cyclobutane-pyrimidine dimers (CPDs), many kinds of living organisms can repair CPDs by photoreactivation (PR) utilizing the near-UV/blue light component in sunlight. Euglena cells are known to possess such PR activity. In the present paper, the formation of CPDs induced by UV-C exposure and the photoreactivation PR repair of these CPDs by UV-A are demonstrated. To clarify the adaptive responses prior UV-B irradiation on PR activity, cells were cultured in the dark or under UV-B light. When the cells were cultured in the dark for 3 d prior to UV-C exposure, PR activity decreased. When the cells were cultured under UV-B light, however, PR activity increased. These results suggest that exposing the cells to UV-B prior to exposure to UV-C induced an adaptive response towards DNA damage caused by UV-C exposure, and this UV-C induced damage was repaired through PR activity. 相似文献
53.
T Suzuki K Narita A Terakita E Takai K Nagai Y Kito Y Tsukahara 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》1999,122(3):369-374
Phospholipase C (PLC) is the key enzyme in the phototransduction cascade of invertebrate rhabdomeric photoreceptors. In addition to 130 kDa PLC, a 95 kDa protein recognized by antibody against the catalytic site of PLC was found in the squid retina. The PLC-like 95 kDa protein (95 kDa PLC) was produced from 130 kDa PLC by an intrinsic protease in the presence of calcium. The 130 kDa PLC was stimulated by the active form of Gq-class G-protein alpha (Gq alpha), but the 95 kDa PLC was not, although their PLC activity was similar. A 35 kDa fragment, the counterpart of 95 kDa PLC, was not recognized by antibodies against catalytic site or N-terminal site of the 130 kDa PLC, indicating that the cleavage site is on the C-terminal side beyond the catalytic site. In the presence of a large excess of the 35 kDa fragment, 95 kDa PLC was stimulated by Gq alpha to a similar extent as intact 130 kDa PLC. These results indicate that the C-terminal polypeptide of PLC is necessary for regulation of its enzyme activity by Gq alpha. The uncoupling of PLC from Gq alpha, caused by limited proteolysis, is therefore a candidate regulatory mechanism of the phototransduction cascade in rhabdomeric photoreceptors. 相似文献
54.
A Double-Strand Break Repair Component Is Essential for S Phase Completion in Fission Yeast Cell Cycling
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Kimihiko Suto Akihisa Nagata Hiroshi Murakami Hiroto Okayama 《Molecular biology of the cell》1999,10(10):3331-3343
Fission yeast rad22(+), a homologue of budding yeast RAD52, encodes a double-strand break repair component, which is dispensable for proliferation. We, however, have recently obtained a cell division cycle mutant with a temperature-sensitive allele of rad22(+), designated rad22-H6, which resulted from a point mutation in the conserved coding sequence leading to one amino acid alteration. We have subsequently isolated rad22(+) and its novel homologue rti1(+) as multicopy suppressors of this mutant. rti1(+) suppresses all the defects of cells lacking rad22(+). Mating type switch-inactive heterothallic cells lacking either rad22(+) or rti1(+) are viable, but those lacking both genes are inviable and arrest proliferation with a cell division cycle phenotype. At the nonpermissive temperature, a synchronous culture of rad22-H6 cells performs DNA synthesis without delay and arrests with chromosomes seemingly intact and replication completed and with a high level of tyrosine-phosphorylated Cdc2. However, rad22-H6 cells show a typical S phase arrest phenotype if combined with the rad1-1 checkpoint mutation. rad22(+) genetically interacts with rad11(+), which encodes the large subunit of replication protein A. Deletion of rad22(+)/rti1(+) or the presence of rad22-H6 mutation decreases the restriction temperature of rad11-A1 cells by 4-6 degrees C and leads to cell cycle arrest with chromosomes incompletely replicated. Thus, in fission yeast a double-strand break repair component is required for a certain step of chromosome replication unlinked to repair, partly via interacting with replication protein A. 相似文献
55.
Birukawa N Ando H Goto M Kanda N Pastene LA Urano A 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2008,149(2):227-235
Urea transport in the kidney is important for the production of concentrated urine. This process is mediated by urea transporters (UTs) encoded by two genes, UT-A (Slc14a2) and UT-B (Slc14a1). Our previous study demonstrated that cetaceans produce highly concentrated urine than terrestrial mammals, and that baleen whales showed higher concentrations of urinary urea than sperm whales. Therefore, we hypothesized that cetaceans have unique actions of UTs to maintain fluid homeostasis in marine habitat. Kidney samples of common minke (Balaenoptera acutorostrata), sei (B. borealis), Bryde's (B. brydei) and sperm whales (Physeter macrocephalus) were obtained to determine the nucleotide sequences of mRNAs encoding UT. The sequences of 2.5-kb cDNAs encode 397-amino acid proteins, which are 90-94% identical to the mammalian UT-A2s. Two putative glycosylation sites are conserved between the whales and the terrestrial mammals, whereas consensus sites for protein kinases are not completely conserved; only a single protein kinase A consensus site was identified in the whale UT-A2s. Two protein kinase C consensus sites are present in the baleen whale UT-A2s, however, a single protein kinase C consensus site was identified in the sperm whale UT-A2. These different phosphorylation sites of whale UT-A2s may result in the high concentrations of urinary urea in whales, by reflecting their urea permeability. 相似文献
56.
Cell death related nuclease 4 (CRN-4) is one of the apoptotic nucleases involved in DNA degradation in Caenorhabditis elegans. To understand how CRN-4 is involved in apoptotic DNA fragmentation, we analyzed CRN-4's biochemical properties, in vivo cell functions, and the crystal structures of CRN-4 in apo-form, Mn(2+)-bound active form, and Er(3+)-bound inactive form. CRN-4 is a dimeric nuclease with the optimal enzyme activity in cleaving double-stranded DNA in apoptotic salt conditions. Both mutational studies and the structures of the Mn(2+)-bound CRN-4 revealed the geometry of the functional nuclease active site in the N-terminal DEDDh domain. The C-terminal domain, termed the Zn-domain, contains basic surface residues ideal for nucleic acid recognition and is involved in DNA binding, as confirmed by deletion assays. Cell death analysis in C. elegans further demonstrated that both the nuclease active site and the Zn-domain are required for crn-4's function in apoptosis. Combining all of the data, we suggest a structural model where chromosomal DNA is bound at the Zn-domain and cleaved at the DEDDh nuclease domain in CRN-4 when the cell is undergoing apoptosis. 相似文献
57.
Hisao Tsukamoto David L. Farrens Mitsumasa Koyanagi Akihisa Terakita 《The Journal of biological chemistry》2009,284(31):20676-20683
Light converts rhodopsin, the prototypical G protein-coupled receptor, into a form capable of activating G proteins. Recent work has shown that the light-activated state of different rhodopsins can possess different molecular properties, especially different abilities to activate G protein. For example, bovine rhodopsin is ∼20-fold more effective at activating G protein than parapinopsin, a non-visual rhodopsin, although these rhodopsins share relatively high sequence similarity. Here we have investigated possible structural aspects that might underlie this difference. Using a site-directed fluorescence labeling approach, we attached the fluorescent probe bimane to cysteine residues introduced in the cytoplasmic ends of transmembrane helices V and VI in both rhodopsins. The fluorescence spectra of these probes as well as their accessibility to aqueous quenching agents changed dramatically upon photoactivation in bovine rhodopsin but only moderately so in parapinopsin. We also compared the relative movement of helices V and VI upon photoactivation of both rhodopsins by introducing a bimane label and the bimane-quenching residue tryptophan into helices VI and V, respectively. Both receptors showed movement in this region upon activation, although the movement appears much greater in bovine rhodopsin than in parapinopsin. Together, these data suggest that a larger conformational change in helices V and VI of bovine rhodopsin explains why it has greater G protein activation ability than other rhodopsins. The different amplitude of the helix movement may also be responsible for functional diversity of G protein-coupled receptors.Rhodopsin, the photosensitive G protein-coupled receptor (GPCR),3 is responsible for transmitting a light signal into an intracellular signaling cascade through activation of G protein in visual and non-visual photoreceptor cells. Rhodopsin consists of a protein moiety (opsin, comprising seven transmembrane α-helical segments) combined with a chromophore (11-cis retinal) that acts as the light-sensitive ligand. Photoisomerization of the 11-cis retinal to the all-trans form induces structural changes in the protein moiety that then enable it to couple with and activate the G protein.The crystal structure of inactive bovine rhodopsin has been extensively investigated (1–3). Recently, a crystal structure of inactive invertebrate squid rhodopsin was also solved (4), and crystal structures of the inactive form of β-adrenergic receptors and A2 adenosine receptor have been reported (5–7). Remarkably, all of these crystal structures exhibit a very similar arrangement for the seven transmembrane helices (4, 8). Together, these facts suggest that the architecture for the inactive form is conserved among rhodopsin-like GPCRs.The structural features of an activated GPCR are much less defined. Thus, a variety of biochemical and biophysical methods, including cross-linking methods (9, 10) and site-directed spin and fluorescence labeling methods (10–13), have been employed to identify the dynamic and structural changes involved in forming the activated state. The data from these studies consistently suggest that some kind of movement of helix VI is involved in the formation of the active state of the rhodopsins. In particular, the cytoplasmic end of helix VI has been proposed to rotate and/or tilt toward helix V (10–13). Remarkably, the recent crystal structures of bovine opsin are consistent with the widely accepted helix motion model. Both the structures of opsin (the ligand-free form of rhodopsin that has partial G protein activation ability) and a complex of opsin with a peptide derived from the G protein C terminus show a movement of helix VI toward helix V, compared with the dark state rhodopsin structure (14, 15). Studies of β-adrenergic and muscarinic receptors also show that agonist binding promotes movement of helix VI toward helix V in these receptors (16, 17). Because the region between the cytoplasmic ends of helices V and VI in various GPCRs is a main site of interaction with G proteins (18), it is possible that movement of helices V and VI leads to formation of a conformation capable of interacting with G protein (19).Together, these studies imply that the active state conformation of GPCRs may be similar. However, a detailed comparison of the active-state conformation for two different GPCRs has never been precisely undertaken in the same laboratory using the same methods.In this context we have been investigating rhodopsins with different functional properties to determine whether their active states have different conformations. Our goal was to determine whether any functional or structural differences in the active states of these GPCRs could be detected under the exact same experimental conditions.Previously, we have found that several rhodopsins, such as an invertebrate rhodopsin and a vertebrate non-visual rhodopsin parapinopsin (20, 21), can be activated not only by light but also by exogenous all-trans retinal acting as a full agonist (22). This is in contrast to vertebrate visual rhodopsins, including bovine rhodopsin, which cannot fully form the active state by direct binding of all-trans retinal (23), although all-trans retinal can fully activate some rhodopsin mutants (24). Other invertebrate rhodopsin (25) and the circadian photoreceptor melanopsin (26) can also bind all-trans retinal directly.Interestingly, the active form of the all-trans retinal-activated rhodopsins exhibit some striking differences in their spectroscopic and biochemical properties compared with vertebrate visual rhodopsins (27). In particular, the efficiency of bovine rhodopsin for activating G protein is ∼20∼50-fold higher than that of parapinopsin and invertebrate rhodopsin. This difference could be related to the difference in position of a specific amino acid residue counterion that is essential for rhodopsin to absorb visible light, namely one at position 113 or 181 (28).4 Further biochemical analyses using chimeric mutants combining rhodopsins with lower and higher G protein activation abilities suggested that the difference in G protein activation ability was because of a structural difference in transmembrane helices in the active states but not because of difference in amino acid sequence of G protein interaction site (29) (Fig. 1, A–C). In addition, the active states of parapinopsin and the invertebrate rhodopsin are thermally stable and can be reconverted to the inactive state by subsequent light absorption, showing photo-regenerable or bistable nature (21, 28), unlike the active state of bovine rhodopsin, which is thermally unstable and cannot revert to the inactive state by subsequent light absorption (30).Open in a separate windowFIGURE 1.Molecular properties and sites of fluorescent probe attachment for bovine rhodopsin and parapinopsin. A, sequence alignment of bovine rhodopsin and parapinopsin. Amino acid residues to which cysteine and fluorescence label were introduced are marked with red. The amino acid residues identical and similar between bovine rhodopsin and parapinopsin are shown with white characters with black and gray background, respectively. Bovine rhodopsin and parapinopsin show 41% sequence identity and 61% similarity. In this paper the residue number of parapinopsin is described by using the bovine rhodopsin numbering system. B and C, comparison of G protein activation ability of rhodopsin and parapinopsin wild type (WT) proteins and loop-replaced mutants. In these mutants the second and/or third cytoplasmic loop was swapped between the two receptors. ParaL2 and ParaL3 indicate mutants of bovine rhodopsin in which second and third loops were replaced with the corresponding loop of parapinopsin, respectively. RhoL2 and RhoL3 indicate mutants of parapinopsin in which the second and third loops were replaced with the corresponding loops of bovine rhodopsin, respectively. ParaL2L3 and RhoL2L3 are mutants of bovine rhodopsin and parapinopsin in which both the second and third loops were swapped, respectively. See Terakita et al. (29) for more details. Data are presented as the means ± S.E. of three separate experiments except for mutants RhoL3, RhoL2L3, and ParaL2L3 (n = 2). D, model of bovine rhodopsin. Amino acid residues which were mutated to cysteine to enable attachment of the fluorescent probe bimane or mutated to tryptophan are indicated. Positions 226, 227, 244, 250, and 251 in the crystal structure of the dark state of bovine rhodopsin (PDB code 1GZM) are shown. E, reaction of the mBBr label with a sulfhydryl group. The mutants labeled with mBBr are named by the number of the residue and the suffix B1. F, reaction of the PDT-bimane with a sulfhydryl group. The mutants labeled with PDT-bimane are named by the number of the residue and the suffix B2. The disulfide linkage between the label and protein can be cleaved using Tris(2-carboxyethyl)phosphine (32).In this study we used site-directed fluorescence labeling (13, 31) to compare the structural features of active states of bovine rhodopsin with lamprey parapinopsin, a UV-sensitive non-visual pigment in the pineal organs (21). Parapinopsin shows relatively high sequence similarity (∼60%) to bovine rhodopsin, yet it has a greatly reduced ability to activate G protein (see Fig. 1, A–C) (21, 28). Using established protocols, we introduced cysteine residues into the cytoplasmic ends of helices V and VI, the region proposed to rearrange upon activation in GPCRs (11, 12, 14, 18). We then site-specifically labeled these cysteines with the small, non-polar fluorescent probe, bimane, and used the spectral properties of these bimane probes to act as reporter groups for environmental changes around their site of attachment upon formation of the photoactivated state for both rhodopsins.In addition, we measured changes in the relative proximity of the cytoplasmic ends of helix VI to helix V in both rhodopsin and parapinopsin using the tryptophan-induced-quenching of bimane (TrIQ-bimane) fluorescence method (31, 32). TrIQ-bimane measures the efficiency of intramolecular fluorescence quenching of bimane caused by tryptophan (Trp), which occurs in a distance-dependent manner. The goal of this study was to determine whether the helices in both receptors moved in the same way during formation of the active state. Our results show that whereas movement of helix VI relative to helix V occurs during formation of the active state for both parapinopsin and bovine rhodopsin, the “amplitude” of the movement is markedly different between the two rhodopsins. 相似文献
58.
Omura T Kaneko M Okuma Y Orba Y Nagashima K Takahashi R Fujitani N Matsumura S Hata A Kubota K Murahashi K Uehara T Nomura Y 《Journal of neurochemistry》2006,99(6):1456-1469
It has been proposed that in autosomal recessive juvenile parkinsonism (AR-JP), a ubiquitin ligase (E3) Parkin, which is involved in endoplasmic reticulum-associated degradation (ERAD), lacks E3 activity. The resulting accumulation of Parkin-associated endothelin receptor-like receptor (Pael-R), a substrate of Parkin, leads to endoplasmic reticulum stress, causing neuronal death. We previously reported that human E3 HRD1 in the endoplasmic reticulum protects against endoplasmic reticulum stress-induced apoptosis. This study shows that HRD1 was expressed in substantia nigra pars compacta (SNC) dopaminergic neurons and interacted with Pael-R through the HRD1 proline-rich region, promoting the ubiquitylation and degradation of Pael-R. Furthermore, the disruption of endogenous HRD1 by small interfering RNA (siRNA) induced Pael-R accumulation and caspase-3 activation. We also found that ATF6 overexpression, which induced HRD1, accelerated and caused Pael-R degradation; the suppression of HRD1 expression by siRNA partially prevents this degradation. These results suggest that in addition to Parkin, HRD1 is also involved in the degradation of Pael-R. 相似文献
59.
Kihara T Ichikawa S Yonezawa T Lee JW Akihisa T Woo JT Michi Y Amagasa T Yamaguchi A 《Biochemical and biophysical research communications》2011,(2):211-217
We investigated the effects of acerogenin A, a natural compound isolated from Acer nikoense Maxim, on osteoblast differentiation by using osteoblastic cells. Acerogenin A stimulated the cell proliferation of MC3T3-E1 osteoblastic cells and RD-C6 osteoblastic cells (Runx2-deficient cell line). It also increased alkaline phosphatase activity in MC3T3-E1 and RD-C6 cells and calvarial osteoblastic cells isolated from the calvariae of newborn mice. Acerogenin A also increased the expression of mRNAs related to osteoblast differentiation, including Osteocalcin, Osterix and Runx2 in MC3T3-E1 cells and primary osteoblasts: it also stimulated Osteocalcin and Osterix mRNA expression in RD-C6 cells. The acerogenin A treatment for 3 days increased Bmp-2, Bmp-4, and Bmp-7 mRNA expression levels in MC3T3-E1 cells. Adding noggin, a BMP specific-antagonist, inhibited the acerogenin A-induced increase in the Osteocalcin, Osterix and Runx2 mRNA expression levels. These results indicated that acerogenin A stimulates osteoblast differentiation through BMP action, which is mediated by Runx2-dependent and Runx2-independent pathways. 相似文献
60.