全文获取类型
收费全文 | 1960篇 |
免费 | 110篇 |
国内免费 | 3篇 |
出版年
2023年 | 3篇 |
2022年 | 13篇 |
2021年 | 19篇 |
2020年 | 13篇 |
2019年 | 18篇 |
2018年 | 23篇 |
2017年 | 30篇 |
2016年 | 45篇 |
2015年 | 58篇 |
2014年 | 72篇 |
2013年 | 102篇 |
2012年 | 111篇 |
2011年 | 146篇 |
2010年 | 81篇 |
2009年 | 112篇 |
2008年 | 149篇 |
2007年 | 130篇 |
2006年 | 124篇 |
2005年 | 134篇 |
2004年 | 113篇 |
2003年 | 129篇 |
2002年 | 137篇 |
2001年 | 31篇 |
2000年 | 24篇 |
1999年 | 17篇 |
1998年 | 24篇 |
1997年 | 20篇 |
1996年 | 26篇 |
1995年 | 19篇 |
1994年 | 17篇 |
1993年 | 9篇 |
1992年 | 12篇 |
1991年 | 7篇 |
1990年 | 12篇 |
1989年 | 10篇 |
1988年 | 11篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 6篇 |
1984年 | 12篇 |
1983年 | 11篇 |
1982年 | 4篇 |
1981年 | 2篇 |
1980年 | 4篇 |
1978年 | 5篇 |
1975年 | 2篇 |
1974年 | 7篇 |
1973年 | 2篇 |
1968年 | 2篇 |
1967年 | 2篇 |
排序方式: 共有2073条查询结果,搜索用时 31 毫秒
991.
Kohji Seio Hisashi Ukawa Koh-ichiro Shohda Mitsuo Sekine 《Journal of biomolecular structure & dynamics》2013,31(6):735-746
Abstract The stacking interactions between a universal base of 3-nitropyrrole (3NP) and four canonical nucleobases were studied by means of ab initio molecular orbital calculations. The stabilities of the complexes are comparable to those of the stacked dimers of canonical bases reported previously. The detailed analysis of the interaction energies revealed the importance of the dipole-dipole interaction included in the Hartree-Fock terms to determine the geometry dependence of the stacking energies. It was also clarified that the dispersion energies included in the electron-correlation terms were essential to obtain adequate stabilities. The contribution of the nitro group was evaluated by the comparative studies of pyrrole and 3NP. The increased molecular dipole moment and surface are expected to account for the enhancement of the stability of the stacked dimers containing 3NP. The force field parameters required for calculation of the molecular mechanics of 3NP were obtained for 3NP on the basis of these molecular orbital calculations. The energy-minimized structures obtained by the molecular mechanics calculations of 3NP accorded with those obtained by the molecular orbital calculations described above. A DNA duplex structure containing 3NP-A, 3NP-T, or 3NP-C was calculated by use of these force field parameters. In the case of 3NP-A, the computationally calculated structure was in good agreement with that previously determined by use of 1H-NMR except for the orientation of the nitro group. 相似文献
992.
Hideyuki Maeda Hisashi Nagai Genzou Takemura Kaori Shintani-Ishida Masaaki Komatsu Sayoko Ogura Toshihiko Aki Mikiayasu Shirai Ichiro Kuwahira Ken-ichi Yoshida 《生物化学与生物物理学报:疾病的分子基础》2013,1832(8):1159-1166
Sleep apnea syndrome (SAS) is considered to be associated with heart failure (HF). It is known that autophagy is induced in various heart diseases thereby promotes survival, but its excess may be maladaptive. Intermittent hypoxia (IH) plays pivotal role in the pathogenesis of SAS. We aimed to clarify the relationships among IH, autophagy, and HF. Rats underwent IH at a rate of 20 cycles/h (nadir of 4% O2 to peak of 21% O2 with 0% CO2) or normal air breathing (control) for 8 h/d for 3 weeks. IH increased the cardiac LC3II/LC3I ratio. The IH induced upregulation of LC3II was attenuated by the administration of an inhibitor of autophagosome formation 3-methyladenine (3-MA), but enhanced by an inhibitor of autophagosome–lysosome fusion chloroquine (CQ), showing enhanced autophagic flux in IH hearts. Electron microscopy confirmed an increase in autophagosomes and lysosomes in IH. With 3-MA or CQ, IH induced progressive deterioration of fractional shortening (FS) on echocardiography over 3 weeks, although IH, 3-MA, or CQ alone had no effects. With CQ, IH for 4 weeks increased serum troponin T levels, reflecting necrosis. Western blotting analyses showed dephosphorylation of Akt and mammalian target of rapamycin (mTOR) at Akt (Ser2448, 2481) sites, suggesting the activation of autophagy via Akt inactivation. Conclusions. IH-mediated autophagy maintains contractile function, whereas when autophagy is inhibited, IH induces systolic dysfunction due to myocyte necrosis. General significance. This study highlighted the potential implications of autophagy in cardio-protection in early SAS patients without comorbidity, reproduced in normal rats by 3 ~ 4 weeks of IH. 相似文献
993.
Hideo Kusaoke Yoshitaka Hayashi Yasuhiro Kadowaki Hisashi Kimoto 《Bioscience, biotechnology, and biochemistry》2013,77(9):2441-2446
It was found that plasmid DNA (pUB 110) can be introduced into not only protoplasts but also intact cells of Bacillus subtilis by electric field pulses. The transformation of, B. subtilis using protoplasts results in an efficiency of 2.5 × 104 transformants per μg of DNA, with a single pulse of 50 jisec with an initial electric field strength of 7kV/cm. Even transformation of intact B. subtilis cells results in a maximum efficiency of 1.5 × 103 transformants per μg DNA, with a single pulse of 400 μsec with an initial electric field strength of 16kV/cm. The cell survival of protoplasts and intact cells was approximately 100% and 30%, respectively, under the conditions found to be optimal for the transformation process. Plasmid DNA isolated from pUB 110 containing transformants was indistinguishable from authentic preparations of pBU 110 on gel electrophoretic analysis. 相似文献
994.
Satoshi Yamauchi Saya Kawahara Tuti Wukirsari Hisashi Nishiwaki Kosuke Nishi Takuya Sugahara Koichi Akiyama Taro Kishida 《Bioorganic & medicinal chemistry letters》2013,23(17):4923-4930
The cytotoxic activities of sesquilignans, (7S,8S,7′R,8′R)- and (7R,8R,7′S,8′S)-morinol A and (7S,8S,7′S,8′S)- and (7R,8R,7′R,8′R)-morinol B were compared, showing no significant difference between stereoisomers (IC50 = 24–35 μM). As a next stage, the effect of substituents at 7, 7′, and 7″-aromatic ring on the activity was evaluated to find out the higher activity of (7S,8S,7′R,8′R)-7,7′,7″-phenyl derivative 18 (IC50 = 6–7 μM). In the research on the structure–activity relationship of 7″-position of (7S,8S,7′R,8′R)-7,7′,7″-phenyl derivative 18, the most potent compounds were 7,7′,7″-phenyl derivative 18 (IC50 = 6 μM) against HeLa cells. Against HL-60 cells, 7″-(4-nitrophenyl)-7,7′-phenyl derivative 33 and 7″-hexyl-7,7′-phenyl derivative 37 (IC50 = 5 μM) showed highest activity. We discovered the compounds showed four to sevenfold potent activity than that of natural (7S,8S,7′R,8′R)-morinol A. It was also confirmed that the 7′-benzylic hydroxy group have an important role for exhibiting activity, on the other hand, the resonance system of cinnamyl structure is not crucial for the potent activity. 相似文献
995.
Seikou Nakamura Souichi Nakashima Genzo Tanabe Yoshimi Oda Nami Yokota Katsuyoshi Fujimoto Takahiro Matsumoto Rika Sakuma Tomoe Ohta Keiko Ogawa Shino Nishida Hisako Miki Hisashi Matsuda Osamu Muraoka Masayuki Yoshikawa 《Bioorganic & medicinal chemistry》2013,21(3):779-787
Methanolic extracts from the flower buds and leaves of sacred lotus (Nelumbo nucifera, Nymphaeaceae) were found to show inhibitory effects on melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. From the methanolic extracts, a new alkaloid, N-methylasimilobine N-oxide, was isolated together with eleven benzylisoquinoline alkaloids. The absolute stereostructure of the new alkaloid was determined from chemical and physicochemical evidence. Among the constituents isolated, nuciferine, N-methylasimilobine, (?)-lirinidine, and 2-hydroxy-1-methoxy-6a,7-dehydroaporphine showed potent inhibition of melanogenesis. Comparison of the inhibitory activities of synthetic related alkaloids facilitated characterization of the structure-activity relationships of aporphine- and benzylisoquinoline-type alkaloids. In addition, 3–30 μM nuciferine and N-methylasimilobine inhibited the expression of tyrosinase mRNA, 3–30 μM N-methylasimilobine inhibited the expression of TRP-1 mRNA, and 10–30 μM nuciferine inhibited the expression of TRP-2 mRNA. 相似文献
996.
Nagatoshi Fujiwara Steven A. Porcelli Takashi Naka Ikuya Yano Shinji Maeda Hirotaka Kuwata Shizuo Akira Satoshi Uematsu Takemasa Takii Hisashi Ogura Kazuo Kobayashi 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2013,1831(6):1177-1184
Sphingobacterium spiritivorum has five unusual sphingophospholipids (SPLs). Our previous study determined the complete chemical structures of these SPLs. The compositions of the long-chain bases/fatty acids in the ceramide portion, isoheptadecasphingosine/isopentadecanoate or isoheptadecasphingosine/2-hydroxy isopentadecanoate, are characteristic. The immune response against bacterial lipid components is considered to play important roles in microbial infections. It is reported that several bacterial sphingolipids composed of ceramide are recognized by CD1-restricted T and NKT cells and that a non-peptide antigen is recognized by γδ T cells. In this study, we demonstrated that these bacterial SPLs activated murine bone marrow macrophages (BMMs) via Toll-like receptor (TLR) 4 but not TLR2, although they slightly activated CD1d-restricted NKT and γδT cells. Interestingly, this TLR 4-recognition pathway of bacterial SPLs involves the fatty acid composition of ceramide in addition to the sugar moiety. A non-hydroxy fatty acid composed of ceramide was necessary to activate murine BMMs. The bacterial survival was significantly higher in TLR4-KO mice than in TLR2-KO and wild-type mice. The results indicate that activation of the TLR4-dependent pathway of BMMs by SPLs induced an innate immune response and contributed to bacterial clearance. 相似文献
997.
Nakatani F Morita YS Ashida H Nagamune K Maeda Y Kinoshita T 《Biochemical and biophysical research communications》2011,(2):421-425
The procyclic stage of Trypanosoma brucei is covered by glycosylphosphatidylinositol (GPI)-anchored surface proteins called procyclins. The procyclin GPI anchor contains a side chain of N-acetyllactosamine repeats terminated by sialic acids. Sialic acid modification is mediated by trans-sialidases expressed on the parasite’s cell surface. Previous studies suggested the presence of more than one active trans-sialidases, but only one has so far been reported. Here we cloned and examined enzyme activities of four additional trans-sialidase homologs, and show that one of them, Tb927.8.7350, encodes another active trans-sialidase, designated as TbSA C2. In an in vitro assay, TbSA C2 utilized α2-3 sialyllactose as a donor, and produced an α2-3-sialylated product, suggesting that it is an α2-3 trans-sialidase. We suggest that TbSA C2 plays a role in the sialic acid modification of the trypanosome cell surface. 相似文献
998.
999.
The misfolding and self-assembly of proteins into amyloid fibrils, which occur in several debilitating and age-related diseases, are affected by common components of amyloid deposits, notably lipids and lipid complexes. Previously, the effects of phospholipids on amyloid fibril formation by apolipoprotein (apo) C-II have been examined, where low concentrations of micellar phospholipids and lipid bilayers induce a new, straight rod-like morphology for apoC-II fibrils. This fibril appearance is distinct from the twisted-ribbon morphology observed when apoC-II fibrils are formed in the absence of lipids. We used total internal reflection fluorescence microscopy (TIRFM) to visualize the described polymorphism of apoC-II amyloid fibrils. The spontaneous assembly of apoC-II into either twisted-ribbon fibrils in the absence of lipids or into fibrils of straight rod-like morphology when lipids are present was captured by TIRFM. The latter was found to be better suited for visualization using TIRFM. The difference between seeding of apoC-II straight fibrils on microscopic quartz slide and in test tube suggested a role for the effects of incubation surface on fibril formation. Seed-dependent growth of apoC-II straight fibrils was probed further by using a dual-labelling construct, giving insights into the straight fibril growth pattern. 相似文献
1000.
Ye F Lemieux H Hoppel CL Hanson RW Hakimi P Croniger CM Puchowicz M Anderson VE Fujioka H Stavnezer E 《The Journal of biological chemistry》2011,286(46):40013-40024