全文获取类型
收费全文 | 1396篇 |
免费 | 86篇 |
出版年
2022年 | 6篇 |
2021年 | 10篇 |
2020年 | 13篇 |
2019年 | 14篇 |
2018年 | 16篇 |
2017年 | 24篇 |
2016年 | 17篇 |
2015年 | 21篇 |
2014年 | 37篇 |
2013年 | 81篇 |
2012年 | 69篇 |
2011年 | 57篇 |
2010年 | 35篇 |
2009年 | 36篇 |
2008年 | 74篇 |
2007年 | 72篇 |
2006年 | 67篇 |
2005年 | 74篇 |
2004年 | 55篇 |
2003年 | 53篇 |
2002年 | 70篇 |
2001年 | 65篇 |
2000年 | 49篇 |
1999年 | 37篇 |
1998年 | 23篇 |
1997年 | 16篇 |
1996年 | 15篇 |
1995年 | 18篇 |
1994年 | 17篇 |
1993年 | 15篇 |
1992年 | 36篇 |
1991年 | 29篇 |
1990年 | 25篇 |
1989年 | 26篇 |
1988年 | 22篇 |
1987年 | 28篇 |
1986年 | 16篇 |
1985年 | 15篇 |
1984年 | 9篇 |
1983年 | 14篇 |
1981年 | 9篇 |
1980年 | 8篇 |
1978年 | 8篇 |
1977年 | 9篇 |
1976年 | 13篇 |
1975年 | 8篇 |
1973年 | 10篇 |
1971年 | 5篇 |
1967年 | 7篇 |
1965年 | 5篇 |
排序方式: 共有1482条查询结果,搜索用时 15 毫秒
991.
Yuichi Hayashi Megumi Yamada Akio Kimura Takahiko Asano Katsuya Satoh Tetsuyuki Kitamoto 《朊病毒》2017,11(6):454-464
We report the case of a 76-year-old woman presenting with 47-month history of progressive dementia and cortical blindness with no family history. Antibodies against thyroid glands and the N-terminus of α-enolase (NAE) were detected in her serum. Neurological examination revealed progressive dementia, frontal signs, visual disturbance, and exaggerated bilateral tendon reflexes in both legs. Diffusion MRI showed cortical hyper-intensities in the bilateral occipital and parietal, and the left frontal and temporal cortices. 99mTc-ethyl cysteinate dimer-single photon emission computed tomography indicated decreased regional cerebral blood flow throughout the bilateral parietal lobes and partially in the left frontal and temporal lobes. PRNP gene analysis showed no mutations with methionine homozygosity at codon 129 in peripheral blood. Cerebrospinal fluid examination, including 14-3-3 and total tau protein detection, revealed normal levels; however, prion proteins were amplified by the real-time quaking-induced conversion method. Hashimoto's encephalopathy was excluded on the basis of unresponsiveness to corticosteroids. The symptoms progressed slowly. Periodic sharp-wave complexes were observed on electroencephalogram 36 months after the onset of symptoms; the patient reached a state of akinetic mutism at 47 months. This was a probable case of MM2-cortical-type sCJD with anti-NAE antibodies based on the World Health Organization (WHO) diagnostic criteria for sCJD, genetic information, and the slowly progressive course. However, this case did not meet with the probable WHO diagnostic criteria until 3 years after symptom onset, highlighting the difficulty of diagnosing a living case of the MM2-type of sCJD. Therefore, establishment of clinical diagnostic criteria for MM2-type of sCJD is required. 相似文献
992.
Asano N Yokoyama K Sakurai M Ikeda K Kizu H Kato A Arisawa M Höke D Dräger B Watson AA Nash RJ 《Phytochemistry》2001,57(5):721-726
Three dihydroxynortropanes, 2alpha,7beta-dihydroxynortropane, 2alpha,3beta-dihydroxynortropane, and 3alpha,7beta-dihydroxynortropane, were isolated from calystegine-producing plants in the families Convolvulaceae and Solanaceae. 2alpha,7beta-Dihydroxynortropane was isolated from six species in the Convolvulaceae whereas only Calystegia soldanella contained it and 2alpha,3beta-dihydroxynortropane. Although neither of these were detectable in three species tested in the Solanaceae, 3alpha,7beta-dihydroxynortropane was, however, isolated from Duboisia leichhardtii. 相似文献
993.
Over one hundred polyhydroxylated alkaloids have been isolated from plants and micro-organisms. These alkaloids can be potent and highly selective glycosidase inhibitors and are arousing great interest as tools to study cellular recognition and as potential therapeutic agents. However, only three of the natural products so far have been widely studied for therapeutic potential due largely to the limited commercial availability of the other compounds. 相似文献
994.
Six4, a putative myogenin gene regulator, is not essential for mouse embryonal development
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Ozaki H Watanabe Y Takahashi K Kitamura K Tanaka A Urase K Momoi T Sudo K Sakagami J Asano M Iwakura Y Kawakami K 《Molecular and cellular biology》2001,21(10):3343-3350
Six4 is a member of the Six family genes, homologues of Drosophila melanogaster sine oculis. The gene is thought to be involved in neurogenesis, myogenesis, and development of other organs, based on its specific expression in certain neuronal cells of the developing embryo and in adult skeletal muscles. To elucidate the biological roles of Six4, we generated Six4-deficient mice by replacing the Six homologous region and homeobox by the beta-galactosidase gene. 5-Bromo-4-chloro-3-indolyl-beta-D-galactopyranoside staining of the heterozygous mutant embryos revealed expression of Six4 in cranial and dorsal root ganglia, somites, otic and nasal placodes, branchial arches, Rathke's pouch, apical ectodermal ridges of limb buds, and mesonephros. The expression pattern was similar to that of Six1 except at the early stage of embryonic day 8.5. Six4-deficient mice were born according to the Mendelian rule with normal gross appearance and were fertile. No hearing defects were detected. Six4-deficient embryos showed no morphological abnormalities, and the expression patterns of several molecular markers, e.g., myogenin and NeuroD3 (neurogenin1), were normal. Our results indicate that Six4 is not essential for mouse embryogenesis and suggest that other members of the Six family seem to compensate for the loss of Six4. 相似文献
995.
Dictyostelium discoideum is a unique experimental organism which allows genetic analysis of the mechanism of cytokinesis of the animal type, and a number of mutations which affect cytokinesis in one way or other have been identified. Myosin II filaments accumulate in the equatorial region, and myosin II-null cells cannot divide in suspension, indicating that active, myosin II-dependent constriction of the cleavage furrow contributes to bisection of the cell. We refer to this method of cytokinesis as cytokinesis A. On substrates, however, myosin II-null cells divide efficiently in a cell cycle-coupled manner. This adhesion-dependent but myosin II-independent division method, which we termed cytokinesis B, is carried out by a pathway that is genetically distinct from that of cytokinesis A. Morphological analyses suggested that cytokinesis B is driven by radial traction forces generated along polar peripheries, which indirectly cause furrow ingression. Identification of two redundant pathways have allowed us to search genes involved in either pathway by mutagenizing cells which are already defective in one of the pathways. This approach enabled us to identify a number of novel cytokinesis-related genes, as well as to reclassify known genes as cytokinesis-related. 相似文献
996.
Single nucleotide polymorphism of human platelet-activating factor receptor impairs G-protein activation 总被引:2,自引:0,他引:2
Fukunaga K Ishii S Asano K Yokomizo T Shiomi T Shimizu T Yamaguchi K 《The Journal of biological chemistry》2001,276(46):43025-43030
Various proinflammatory and vasoactive actions of platelet-activating factor (PAF) are mediated through a specific G-protein-coupled PAF receptor (PAFR). We identified a novel DNA variant in the human PAFR gene, which substitutes an aspartic acid for an alanine residue at position 224 (A224D) in the putative third cytoplasmic loop. This mutation was observed in a Japanese population at an allele frequency of 7.8%. To delineate the functional consequences of this structural alteration, Chinese hamster ovary cells were stably transfected with constructs encoding either wild-type or A224D mutated PAFR. No significant difference was observed in the expression level of the receptor or the affinity to PAF or to an antagonist, WEB2086, between the cells transfected with wild-type and mutant PAFR. Chinese hamster ovary cells expressing A224D mutant PAFR displayed partial but significant reduction of PAF-induced intracellular signals such as calcium mobilization, inositol phosphate production, inhibition of adenylyl cyclase, and chemotaxis. These findings suggest that this variant receptor produced by a naturally occurring mutation exhibits impaired coupling to G-proteins and may be a basis for interindividual variation in PAF-related physiological responses, disease predisposition or phenotypes, and drug responsiveness. 相似文献
997.
Tulin EE Onoda N Maeda M Hasegawa M Nosaka T Nomura H Asano S Kitamura T 《The Journal of biological chemistry》2001,276(29):27519-27526
In the search for stromal-derived growth factors, we have identified a novel secreted short form of immune suppressor factor (ISF) using a combination of a genetic approach and retrovirus-mediated functional screening. This protein, which we termed ShIF, was isolated based on its ability to support proliferation of a mutant clone S21, which was established from Ba/F3 cells that are usually interleukin-3-dependent but became dependent on a stroma cell line ST2 after chemical mutagenesis. ISF, a membrane protein harboring six transmembrane domains, was reported to have immunosuppressive functions. The coding region of ShIF started from the third transmembrane domain of ISF. Biochemical analysis demonstrated that ShIF was expressed in both the secreted and membrane-bound forms of 27-kDa protein, which was supposed to have an internal ATG present in the third transmembrane domain of ISF as a start codon. In addition to the full-length form of ISF, a major protein with a molecular size of 27 kDa was also expressed through the proteolytic process of ISF. ShIF resembles this naturally occurring short form of ISF (sISF). Deletion analysis of the major domains of ISF cDNA revealed that ShIF is an active functional domain of ISF with a capability to support proliferation of S21 cells. Enforced expression of ShIF in MS10 cells, bone marrow stroma cells that do not express endogenous ShIF or ISF, conferred on the cells an ability to support the growth of S21 cells as well as bone marrow cells. Interestingly, ShIF shows a high sequence homology to the C-terminal part of a 95-kDa yeast vacuolar H (+)-ATPase subunit, Vph1p (39%), and a 116-kDa proton pump (VPP1) (54%) of the rat and bovine synaptic vesicle. Therefore, it is possible that ShIF also acts as a proton pump and somehow prevents the cells from undergoing apoptosis. 相似文献
998.
Ijuin T Mochizuki Y Fukami K Funaki M Asano T Takenawa T 《The Journal of biological chemistry》2000,275(15):10870-10875
We have identified a cDNA encoding a novel inositol polyphosphate 5-phosphatase. It contains two highly conserved catalytic motifs for 5-phosphatase, has a molecular mass of 51 kDa, and is ubiquitously expressed and especially abundant in skeletal muscle, heart, and kidney. We designated this 5-phosphatase as SKIP (Skeletal muscle and Kidney enriched Inositol Phosphatase). SKIP is a simple 5-phosphatase with no other motifs. Baculovirus-expressed recombinant SKIP protein exhibited 5-phosphatase activities toward inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, phosphatidylinositol (PtdIns) 4,5-bisphosphate, and PtdIns 3,4, 5-trisphosphate but has 6-fold more substrate specificity for PtdIns 4,5-bisphosphate (K(m) = 180 microM) than for inositol 1,4, 5-trisphosphate (K(m) = 1.15 mM). The ectopic expression of SKIP protein in COS-7 cells and immunostaining of neuroblastoma N1E-115 cells revealed that SKIP is expressed in cytosol and that loss of actin stress fibers occurs where the SKIP protein is concentrated. These results imply that SKIP plays a negative role in regulating the actin cytoskeleton through hydrolyzing PtdIns 4,5-bisphosphate. 相似文献
999.
Watari K Tojo A Nagamura-Inoue T Nagamura F Takeshita A Fukushima T Motoji T Tani K Asano S 《FEBS letters》2000,466(2-3):367-371
In order to elucidate molecular events in BCR/ABL-induced transformation, we adopted a polymerase chain reaction (PCR)-based technique of differential display and compared mRNA expression in human factor-dependent cells, TF-1, with that in factor-independent cells, ID-1, which were established from TF-1 cells by transfection of BCR/ABL. Cloning and sequencing of a gene which was upregulated in ID-1 cells revealed that the gene was identical to a melanoma antigen, PRAME. Our present study demonstrated that PRAME was markedly expressed in primary leukemic cells with chronic myeloid leukemia (CML) in blastic crisis and Philadelphia (Ph)+-acute lymphoblastic leukemia (ALL), in which BCR/ABL played an important role as a pathogenic gene. Moreover, comparison of PRAME expression among CD34+ cells with CML in blastic, accelerated, and chronic phases revealed a higher expression in CML in advanced phases. Thus PRAME was considered to be a good candidate for a marker of Ph+-leukemic blast cells as well as a new target antigen of leukemic blast cells that cytotoxic T cells can recognize. 相似文献
1000.
A region of the sulfonylurea receptor critical for a modulation of ATP-sensitive K(+) channels by G-protein betagamma-subunits
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Wada Y Yamashita T Imai K Miura R Takao K Nishi M Takeshima H Asano T Morishita R Nishizawa K Kokubun S Nukada T 《The EMBO journal》2000,19(18):4915-4925
To determine the interaction site(s) of ATP-sensitive K(+) (K(ATP)) channels for G-proteins, sulfonylurea receptor (SUR2A or SUR1) and pore-forming (Kir6.2) subunits were reconstituted in the mammalian cell line, COS-7. Intracellular application of the G-protein betagamma2-subunits (G(betagamma)(2)) caused a reduction of ATP-induced inhibition of Kir6.2/SUR channel activities by lessening the ATP sensitivity of the channels. G(betagamma)(2) bound in vitro to both intracellular (loop-NBD) and C-terminal segments of SUR2A, each containing a nucleotide-binding domain (NBD). Furthermore, a single amino acid substitution in the loop-NBD of SUR (Arg656Ala in SUR2A or Arg665Ala in SUR1) abolished the G(betagamma)(2)-dependent alteration of the channel activities. These findings provide evidence that G(betagamma) modulates K(ATP) channels through a direct interaction with the loop-NBD of SUR. 相似文献