全文获取类型
收费全文 | 1906篇 |
免费 | 90篇 |
国内免费 | 1篇 |
专业分类
1997篇 |
出版年
2023年 | 6篇 |
2022年 | 13篇 |
2021年 | 26篇 |
2020年 | 16篇 |
2019年 | 26篇 |
2018年 | 31篇 |
2017年 | 21篇 |
2016年 | 43篇 |
2015年 | 51篇 |
2014年 | 72篇 |
2013年 | 142篇 |
2012年 | 135篇 |
2011年 | 125篇 |
2010年 | 84篇 |
2009年 | 66篇 |
2008年 | 142篇 |
2007年 | 118篇 |
2006年 | 105篇 |
2005年 | 138篇 |
2004年 | 125篇 |
2003年 | 129篇 |
2002年 | 114篇 |
2001年 | 14篇 |
2000年 | 21篇 |
1999年 | 15篇 |
1998年 | 26篇 |
1997年 | 26篇 |
1996年 | 20篇 |
1995年 | 14篇 |
1994年 | 16篇 |
1993年 | 7篇 |
1992年 | 13篇 |
1991年 | 13篇 |
1990年 | 12篇 |
1989年 | 8篇 |
1988年 | 6篇 |
1987年 | 7篇 |
1986年 | 3篇 |
1985年 | 7篇 |
1984年 | 7篇 |
1983年 | 6篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1975年 | 2篇 |
1973年 | 2篇 |
1970年 | 2篇 |
1968年 | 3篇 |
排序方式: 共有1997条查询结果,搜索用时 15 毫秒
121.
An environmentally benign and stereoselective beta-mannopyranosylation has been developed employing 4,6-O-benzylidene-protected mannopyranosyl diethyl phosphite as a glycosyl donor and montmorillonite K-10 as an activator. 相似文献
122.
Growth and differentiation potential of main- and side-population cells derived from murine skeletal muscle 总被引:9,自引:0,他引:9
Tamaki T Akatsuka A Okada Y Matsuzaki Y Okano H Kimura M 《Experimental cell research》2003,291(1):83-90
Skeletal muscle-derived CD34+/45- (Sk-34) cells were identified as a new candidate for stem cells. However, the relationship between Sk-34 cells and side-population (SP) cells is unknown. Here, we demonstrate that Sk-34 cells prepared from murine skeletal muscles consist wholly of main-population (MP) cells. The Sk-34 cells included only a few SP cells (1:1000, SP:MP). Colony-forming units of Sk-34 cells of both SP and MP possessed the same potential to differentiate into adipocytes, endothelial, and myogenic cells and showed the same colony-forming activity (1.6%). In addition, the colony-forming units of the CD34-/45- (double negative: DN) population were found to begin CD34 expression and to possess the potential to differentiate into myogenic and endothelial cells. We also found that expression of CD34 antigen precedes MyoD expression during the myogenic process of DN cells. Furthermore, both Sk-34 and DN cell populations were mostly negative for CD73 (93-95%), whereas the CD45+ cell population was >25% positive for CD73, and this trend was also seen in bone marrow-derived CD45+ cells. These results indicate that the MP cell population is about 99.9% responsible for the reported in vitro myogenic-endothelial responses of skeletal muscle-derived cells. 相似文献
123.
Fujimoto Z Kaneko S Momma M Kobayashi H Mizuno H 《The Journal of biological chemistry》2003,278(22):20313-20318
alpha-Galactosidases catalyze the hydrolysis of alpha-1,6-linked galactosyl residues from galacto-oligosaccharides and polymeric galacto-(gluco)mannans. The crystal structure of rice alpha-galactosidase has been determined at 1.5A resolution using the multiple isomorphous replacement method. The structure consisted of a catalytic domain and a C-terminal domain and was essentially the same as that of alpha-N-acetylgalactosaminidase, which is the same member of glycosyl hydrolase family 27. The catalytic domain had a (beta/alpha)8-barrel structure, and the C-terminal domain was made up of eight beta-strands containing a Greek key motif. The structure was solved as a complex with d-galactose, providing a mode of substrate binding in detail. The d-galactose molecule was found bound in the active site pocket on the C-terminal side of the central beta-barrel of the catalytic domain. The d-galactose molecule consisted of a mixture of two anomers present in a ratio equal to their natural abundance. Structural comparisons of rice alpha-galactosidase with chicken alpha-N-acetylgalactosaminidase provided further understanding of the substrate recognition mechanism in these enzymes. 相似文献
124.
Hyaluronan oligosaccharides induce CD44 cleavage and promote cell migration in CD44-expressing tumor cells 总被引:9,自引:0,他引:9
Sugahara KN Murai T Nishinakamura H Kawashima H Saya H Miyasaka M 《The Journal of biological chemistry》2003,278(34):32259-32265
CD44 is an adhesion molecule that serves as a cell surface receptor for several extracellular matrix components, including hyaluronan (HA). The proteolytic cleavage of CD44 from the cell surface plays a critical role in the migration of tumor cells. Although this cleavage can be induced by certain stimuli such as phorbol ester and anti-CD44 antibodies in vitro, the physiological inducer of CD44 cleavage in vivo is unknown. Here, we demonstrate that HA oligosaccharides of a specific size range induce CD44 cleavage from tumor cells. Fragmented HA containing 6-mers to 14-mers enhanced CD44 cleavage dose-dependently by interacting with CD44, whereas a large polymer HA failed to enhance CD44 cleavage, although it bound to CD44. Examination using uniformly sized HA oligosaccharides revealed that HAs smaller than 36 kDa significantly enhanced CD44 cleavage. In particular, the 6.9-kDa HA (36-mers) not only enhanced CD44 cleavage but also promoted tumor cell motility, which was completely inhibited by an anti-CD44 monoclonal antibody. These results raise the possibility that small HA oligosaccharides, which are known to occur in various tumor tissues, promote tumor invasion by enhancing the tumor cell motility that may be driven by CD44 cleavage. 相似文献
125.
Taura Ki K Yamada H Naito E Ariyoshi N Mori Ma MA Oguri K 《Archives of biochemistry and biophysics》2002,402(2):275-280
The kinetics of the association between cytochrome P450 (P450) and microsomal epoxide hydrolase (mEH) was studied by means of resonant mirror based on the principle of surface plasmon resonance. The dissociation equilibrium constants (K(D)) for the affinity of P450 enzymes for mEH were estimated by resonant mirror using an optical biosensor cell covalently bound to rat mEH. Comparable K(D) values were obtained for CYP1A1 and 2B1, and these were greater by one order of magnitude than that for the CYP2C11. To clarify the influences of P450 enzymes on the catalytic activity of mEH, the hydrolyzing activity for styrene oxide and benzo(a)pyrene-7,8-oxide [B(a)P-oxide] was analyzed in the presence or absence of P450s. Styrene oxide hydrolysis was activated by all P450s including the CYP1A, 2B, 2C, and 3A subfamilies. In agreement with the association affinity determined by resonant mirror, CYP2C11 tends to have enhanced activity for styrene oxide hydrolysis. On the other hand, B(a)P-oxide hydrolysis was enhanced by only CYP2C11 while CYP1A1 and CYP2B1 had no effect. These results suggest that (1) many P450 enzymes associate nonspecifically with mEH, (2) the CYP2C11 plays a greater role in the association/activation of mEH and (3) the P450-mediated activation of mEH depends upon the substrate of mEH. 相似文献
126.
Takeuchi H Kobayashi Y Ishigaki S Doyu M Sobue G 《The Journal of biological chemistry》2002,277(52):50966-50972
The mutations in superoxide dismutase 1 (SOD1) cause approximately 20% of familial amyotrophic lateral sclerosis cases. A toxic gain of function has been considered to be the cause of the disease, but its molecular mechanism remains uncertain. To determine whether the subcellular localization of mutant SOD1 is crucial to mutant SOD1-mediated cell death, we produced neuronal cell models with accumulation of SOD1 in each subcellular fraction/organelle, such as the cytosol, nucleus, endoplasmic reticulum, and mitochondria. We showed that the localization of mutant SOD1 in the mitochondria triggered the release of mitochondrial cytochrome c followed by the activation of caspase cascade and induced neuronal cell death without cytoplasmic mutant SOD1 aggregate formation. Nuclear and endoplasmic reticulum localization of mutant SOD1 did not induce cell death. These results suggest that the localization of mutant SOD1 in the mitochondria is critical in the pathogenesis of mutant SOD1-associated familial amyotrophic lateral sclerosis. 相似文献
127.
Sato Y Nabeta Y Tsukahara T Hirohashi Y Syunsui R Maeda A Sahara H Ikeda H Torigoe T Ichimiya S Wada T Yamashita T Hiraga H Kawai A Ishii T Araki N Myoui A Matsumoto S Umeda T Ishii S Kawaguchi S Sato N 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(3):1611-1618
To investigate the immunogenic property of peptides derived from the synovial sarcoma-specific SYT-SSX fusion gene, we synthesized four peptides according to the binding motif for HLA-A24. The peptides, SS391 (PYGYDQIMPK) and SS393 (GYDQIMPKK), were derived from the breakpoint of SYT-SSX, and SS449a (AWTHRLRER) and SS449b (AWTHRLRERK) were from the SSX region. These peptides were tested for their reactivity with CTL precursors (CTLps) in 16 synovial sarcoma patients using HLA-A24/SYT-SSX peptide tetramers and also for induction of specific CTLs from four HLA-A24(+) synovial sarcoma patients. Tetramer analysis indicated that the increased CTLp frequency to the SYT-SSX was associated with pulmonary metastasis in synovial sarcoma patients (p < 0.03). CTLs were induced from PBLs of two synovial sarcoma patients using the peptide mixture of SS391 and SS393, which lysed HLA-A24(+) synovial sarcoma cells expressing SYT-SSX as well as the peptide-pulsed target cells in an HLA class I-restricted manner. These findings suggest that aberrantly expressed SYT-SSX gene products have primed SYT-SSX-specific CTLps in vivo and increased their frequency in synovial sarcoma patients. The identification of SYT-SSX peptides may offer an opportunity to design peptide-based immunotherapeutic approaches for HLA-A24(+) patients with synovial sarcoma. 相似文献
128.
Shamloula HK Mbogho MP Pimentel AC Chrzanowska-Lightowlers ZM Hyatt V Okano H Venkatesh TR 《Genetics》2002,161(2):693-710
In the developing Drosophila eye, cell fate determination and pattern formation are directed by cell-cell interactions mediated by signal transduction cascades. Mutations at the rugose locus (rg) result in a rough eye phenotype due to a disorganized retina and aberrant cone cell differentiation, which leads to reduction or complete loss of cone cells. The cone cell phenotype is sensitive to the level of rugose gene function. Molecular analyses show that rugose encodes a Drosophila A kinase anchor protein (DAKAP 550). Genetic interaction studies show that rugose interacts with the components of the EGFR- and Notch-mediated signaling pathways. Our results suggest that rg is required for correct retinal pattern formation and may function in cell fate determination through its interactions with the EGFR and Notch signaling pathways. 相似文献
129.
Shuichiro Ito Tomoko Takayama Hiroyuki Hanzawa Kimihisa Ichikawa Jun Ohsumi Nobufusa Serizawa Tadashi Hata Hideyuki Haruyama 《Journal of biochemistry》2002,131(1):137-143
Binding of Fas ligand to Fas induces apoptosis. The Fas-Fas ligand system plays important roles in many biological processes, including the elimination of autoreactive lymphoid cells. The mouse anti-human Fas monoclonal antibody HFE7A (m-HFE7A), which induces apoptosis, has been humanized based on a structure predicted by homology modeling. A version of humanized HFE7A is currently under development for the treatment of autoimmune diseases such as rheumatoid arthritis. For a deeper understanding of the protein engineering aspect of antibody humanization, for which information on the three-dimensional structure is essential, we determined the crystal structure of the m-HFE7A antigen-binding fragment (Fab) by X-ray crystallography at 2.5 A resolution. The main-chain conformation of the five loops in the six complementarity-determining regions (CDRs) was correctly predicted with root-mean-square deviations of 0.30-1.04 A based on a comparison of the crystal structure with the predicted structure. The CDR-H3 conformation of the crystal structure, which was not classified as one of the canonical structures, was completely different from that of the predicted structure but adopted the conformation which followed the "H3-rules." The results of charge distribution analysis of the antigen-binding site suggest that electrostatic interactions may be important for its binding to Fas. 相似文献
130.
Expression of programmed death 1 ligands by murine T cells and APC 总被引:31,自引:0,他引:31
Yamazaki T Akiba H Iwai H Matsuda H Aoki M Tanno Y Shin T Tsuchiya H Pardoll DM Okumura K Azuma M Yagita H 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(10):5538-5545
Programmed death 1 (PD-1) is a new member of the CD28/CTLA-4 family, which has been implicated in the maintenance of peripheral tolerance. Two ligands for PD-1, namely, B7-H1 (PD-L1) and B7-DC (PD-L2), have recently been identified as new members of the B7 family but their expression at the protein level remains largely unknown. To characterize the expression of B7-H1 and B7-DC, we newly generated an anti-mouse B7-H1 mAb (MIH6) and an anti-mouse B7-DC mAb (TY25). MIH6 and TY25 immunoprecipitated a single molecule of 43 and 42 kDa from the lysate of B7-H1 and B7-DC transfectants, respectively. Flow cytometric analysis revealed that B7-H1 was broadly expressed on the surface of mouse tumor cell lines while the expression of B7-DC was rather restricted. PD-1 was expressed on anti-CD3-stimulated T cells and anti-IgM plus anti-CD40-stimulated B cells at high levels but was undetectable on activated macrophages or DCs. B7-H1 was constitutively expressed on freshly isolated splenic T cells, B cells, macrophages, and dendritic cells (DCs), and up-regulated on T cells by anti-CD3 stimulation on macrophages by LPS, IFN-gamma, GM-CSF, or IL-4, and on DCs by IFN-gamma, GM-CSF, or IL-4. In contrast, B7-DC expression was only inducible on macrophages and DCs upon stimulation with IFN-gamma, GM-CSF, or IL-4. The inducible expression of PD-1 ligands on both T cells and APCs may suggest new paradigms of PD-1-mediated immune regulation. 相似文献