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81.
Synthesis of 3'-3', 5-5', and 3'-5' dimeric thymidine, linked by an olefinic chain between glycosidic moieties is described. Cross metathesis reaction of 3' or 5' O-allyl analogues of thymidine led to the expected 3'-3' and 5'-5' dimeric compounds, respectively. In order to obtain the 3'-5' dimer, 5'-O-allyl and 3'-O-allyl monomers were first linked by their free 3' OH and 5' OH groups through a glutaryl spacer; ring closing metathesis was then operated upon this temporary dimer, followed by glutaryl removal. 相似文献
82.
Fujioka Y Arano Y Ono M Uehara T Ogawa K Namba S Saga T Nakamoto Y Mukai T Konishi J Saji H 《Bioconjugate chemistry》2001,12(2):178-185
Renal localization of radiolabeled antibody fragments constitutes a problem in targeted imaging and radiotherapy. Recently, we reported use of a novel radioiodination reagent, 3'-[131I]iodohippuryl N(epsilon)-maleoyl-L-lysine (HML), that liberates m-iodohippuric acid before antibody fragments are incorporated into renal cells. In mice, HML-conjugated Fab demonstrated low renal radioactivity levels from early postinjection times. In this study, renal metabolism of HML-conjugated Fab fragments prepared by different thiolation chemistries and by direct radioiodination were investigated to determine the mechanisms responsible for the low renal radioactivity levels. Fab fragments were thiolated by 2-iminothiolane modification or by reduction of disulfide bonds in the Fab fragments, followed by conjugation with radioiodinated HML to prepare [131I]HML-IT-Fab and [125I]HML-Fab, respectively. In biodistribution studies in mice, both [131I]HML-IT-Fab and [125I]HML-Fab demonstrated significantly lower renal radioactivity levels than those of [125I]Fab. In subcellular distribution studies, [125I]Fab showed migration of radioactivity from the membrane to the lysosomal fraction of the renal cells from 10 to 30 min postinjection. On the other hand, the majority of the radioactivity was detected only in the membrane fraction at the same time points after injection of both [131I]HML-IT-Fab and [125I]HML-Fab. In metabolic studies, while [125I]Fab remained intact at 10 min postinjection, both HML-conjugated Fab fragments generated m-iodohippuric acid as a radiometabolite at the same postinjection time. [131I]HML-IT-Fab registered two radiometabolites (intact [131I]HML-IT-Fab and m-iodohippuric acid), whereas additional radiometabolites were observed with [125I]HML-Fab. This suggested that metabolism of both HML-conjugated Fab fragments would occur in the membrane fractions of the renal cells. The findings of this study reinforced our previous hypothesis that radiochemical design of antibody fragments that liberate radiometabolites that are excreted into the urine by the action of brush border enzymes would constitute a useful strategy to reduce renal radioactivity levels from early postinjection times. 相似文献
83.
84.
Roberta J. Ward Stephanie Wilmet Rachida Legssyer Daniel Leroy Louise Toussaint Robert R. Crichton Christophe Pierreux Louis Hue Jacques Piette Surjit Kaila Srai Nita Solanky Dominique Klein Karl Summer 《Biometals》2009,22(2):211-223
The effects of changes in macrophage iron status, induced by single or multiple iron injections, iron depletion or pregnancy,
on both immune function and mRNA expression of genes involved in iron influx and egress have been evaluated. Macrophages isolated
from iron deficient rats, or pregnant rats at day 21 of gestation, either supplemented with a single dose of iron dextran,
10 mg, at the commencement of pregnancy, or not, showed significant increases of macrophage ferroportin mRNA expression, which was paralleled by significant decreases in hepatic Hamp mRNA expression. IRP activity in macrophages was not significantly altered by iron status or the inducement of pregnancy
± a single iron supplement. Macrophage immune function was significantly altered by iron supplementation and pregnancy. Iron
supplementation, alone or combined with pregnancy, increased the activities of both NADPH oxidase and nuclear factor kappa
B (NFκB). In contrast, the imposition of pregnancy reduced the ability of these parameters to respond to an inflammatory stimuli.
Increasing iron status, if only marginally, will reduce the ability of macrophages to mount a sustained response to inflammation
as well as altering iron homeostatic mechanisms. 相似文献
85.
Ludovic Colombeau Karine Teste Amel Hadj-Bouazza Vincent Chaleix Rachida Zerrouki Michel Kraemer 《Nucleosides, nucleotides & nucleic acids》2013,32(2):110-120
The synthesis and biological activity of chloroethyl pyrimidine nucleosides is presented. One of these new nucleosides analogues significantly inhibited cell proliferation, migration and invasion as tested in vitro on the A431 vulvar epidermal carcinoma cell line. 相似文献
86.
Okita K Matsumura Y Sato Y Okada A Morizane A Okamoto S Hong H Nakagawa M Tanabe K Tezuka K Shibata T Kunisada T Takahashi M Takahashi J Saji H Yamanaka S 《Nature methods》2011,8(5):409-412
We report a simple method, using p53 suppression and nontransforming L-Myc, to generate human induced pluripotent stem cells (iPSCs) with episomal plasmid vectors. We generated human iPSCs from multiple donors, including two putative human leukocyte antigen (HLA)-homozygous donors who match ~20% of the Japanese population at major HLA loci; most iPSCs are integrated transgene-free. This method may provide iPSCs suitable for autologous and allologous stem-cell therapy in the future. 相似文献
87.
Kenji Matsumura Masahiro Ono Masashi Yoshimura Hiroyuki Kimura Hiroyuki Watanabe Yoko Okamoto Masafumi Ihara Ryosuke Takahashi Hideo Saji 《Bioorganic & medicinal chemistry》2013,21(11):3356-3362
This paper describes the synthesis and biological evaluation of styrylbenzimidazole (SBIM) derivatives as agents for imaging neurofibrillary tangles (NFT) in patients with Alzheimer’s disease (AD). SBIM derivatives were prepared with 4-iodobenzene-1,2-diamine and substituted cinnamaldehydes. In binding experiments using recombinant tau and Aβ1–42 aggregates, SBIM-3 showed higher affinity for the tau aggregates than Aβ1–42 aggregates (ratio of Kd values was 2.73). In in vitro autoradiography and fluorescent staining, [125I]SBIM-3 (or SBIM-3) bound NFT in sections of AD brain tissue. In biodistribution experiments using normal mice, all [125I]SBIM derivatives showed high initial uptake into (3.20–4.11%ID/g at 2 min after the injection) and rapid clearance from (0.12–0.33%ID/g at 60 min after the injection) the brain. In conclusion, appropriate structural modifications of SBIM derivatives could lead to more useful agents for the in vivo imaging of NFT in AD brains. 相似文献
88.
Integrin α9β1 mediates accelerated cell adhesion and migration through interactions with a number of diverse extracellular ligands. We have shown previously that it directly binds the vascular endothelial growth factors (VEGF) A, C, and D and contributes to VEGF-induced angiogenesis and lymphangiogenesis. Until now, the α9β1 binding site in VEGF has not been identified. Here, we report that the three-amino acid sequence, EYP, encoded by exon 3 of VEGF-A is essential for binding of VEGF to integrin α9β1 and induces adhesion and migration of endothelial and cancer cells. EYP is specific for α9β1 binding and neither requires nor activates VEGFR-2, the cognate receptor for VEGF-A. Following binding to EYP, integrin α9β1 transduces cell migration through direct activation of the integrin signaling intermediates Src and focal adhesion kinase. This interaction is biologically important because it mediates in vitro endothelial cell tube formation, wound healing, and cancer cell invasion. These novel findings identify EYP as a potential site for directed pharmacotherapy. 相似文献
89.
Mukai T Hagimori M Arimitsu K Katoh T Ukon M Kajimoto T Kimura H Magata Y Miyoshi E Taniguchi N Node M Saji H 《Bioorganic & medicinal chemistry》2011,19(14):4312-4321
N-acetylglucosaminyltransferase V (GnT-V) is one of the most relevant glycosyltransferases to tumor invasion and metastasis. Based on previous findings of molecular recognition between GnT-V and synthetic substrates, we designed and synthesized a p-iodophenyl-derivatized trisaccharide, 2-(4-iodophenyl)ethyl 6-O-[2-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-α-d-mannopyranosyl]-β-D-glucopyranoside (IPGMG, 1) and its radiolabeled form, [(125)I]IPGMG ([(125)I]1), for use in assays of GnT-V activity in vitro. The tributyltin derivative, 2-[4-(n-tributylstannyl)phenyl]ethyl 6-O-[2-O-(3,4,6-tri-O-acetyl-2-acetamido-2-deoxy-β-D-glucopyranosyl)-3,4,6-tri-O-acetyl-α-D-mannopyranosyl]-2,3,4-tri-O-acetyl-β-D-glucopyranoside (21), was synthesized as a precursor for the preparation of [(125)I]1. The iododestannylation of 21 using hydrogen peroxide as an oxidant followed by deacetylation yielded [(125)I]1. When [(125)I]1 was incubated in GnT-V-expressing cells with a UDP-GlcNAc donor, the production of β1-6GlcNAc-bearing IPGMG (IPGGMG, 2) was confirmed by radio-HPLC. In kinetic analysis, 1 was found to be a good substrate with a K(m) of 23.7 μM and a V(max) of 159 pmol/h. μg protein. [(125)I]1 would therefore be a useful synthetic substrate for the quantitative determination of GnT-V activity. 相似文献
90.
Phytochelatins (PCs) are heavy metal binding peptides that play an important role in sequestration and detoxification of heavy
metals in plants. In this study, our goal was to develop transgenic plants with increased tolerance for and accumulation of
heavy metals from soil by expressing an Arabidopsis
thaliana
AtPCS1 gene, encoding phytochelatin synthase (PCS), in Indian mustard (Brassica juncea L.). A 35S promoter fused to a FLAG–tagged AtPCS1 cDNA was expressed in Indian mustard, and transgenic lines, designated pc lines, were evaluated for tolerance to and accumulation
of Cd and Zn. Transgenic plants with moderate AtPCS1 expression levels showed significantly higher tolerance to Cd and Zn
stress, but accumulated significantly less Cd and Zn than wild type plants in both shoot and root tissues. However, transgenic
plants with highest expression of the transgene did not exhibit enhanced Cd and Zn tolerance. Shoots of Cd-treated pc plants
had significantly higher levels of phytochelatins and thiols than wild-type plants. Significantly lower concentrations of
gluthatione in Cd-treated shoot and root tissues of transgenic plants were observed. Moderate expression levels of phytochelatin
synthase improved the ability of Indian mustard to tolerate certain levels of heavy metals, but at the same time did not increase
the accumulation potential for Cd and Zn. 相似文献