全文获取类型
收费全文 | 1233篇 |
免费 | 79篇 |
国内免费 | 1篇 |
专业分类
1313篇 |
出版年
2023年 | 3篇 |
2022年 | 9篇 |
2021年 | 14篇 |
2020年 | 5篇 |
2019年 | 5篇 |
2018年 | 11篇 |
2017年 | 17篇 |
2016年 | 19篇 |
2015年 | 27篇 |
2014年 | 44篇 |
2013年 | 60篇 |
2012年 | 48篇 |
2011年 | 76篇 |
2010年 | 44篇 |
2009年 | 41篇 |
2008年 | 75篇 |
2007年 | 78篇 |
2006年 | 84篇 |
2005年 | 79篇 |
2004年 | 64篇 |
2003年 | 48篇 |
2002年 | 73篇 |
2001年 | 31篇 |
2000年 | 32篇 |
1999年 | 29篇 |
1998年 | 14篇 |
1997年 | 15篇 |
1996年 | 26篇 |
1995年 | 12篇 |
1994年 | 14篇 |
1993年 | 17篇 |
1992年 | 16篇 |
1991年 | 14篇 |
1990年 | 17篇 |
1989年 | 14篇 |
1988年 | 10篇 |
1987年 | 9篇 |
1986年 | 9篇 |
1985年 | 7篇 |
1984年 | 19篇 |
1983年 | 12篇 |
1982年 | 9篇 |
1981年 | 15篇 |
1979年 | 12篇 |
1978年 | 3篇 |
1976年 | 4篇 |
1975年 | 4篇 |
1974年 | 3篇 |
1973年 | 6篇 |
1970年 | 4篇 |
排序方式: 共有1313条查询结果,搜索用时 15 毫秒
141.
Immunohistochemical Localization of Ca2+ /Calmodulin-Dependent Protein Kinase II in Rat Brain and Various Tissues 总被引:6,自引:0,他引:6
Polyclonal antibodies against Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) of rat brain were prepared by immunizing rabbits and then purified by antigen-affinity column. The antibodies which recognized both subunits of the enzyme with Mrs 49K and 60K were used for the study on the distribution of CaM kinase II in formalin-fixed, paraffin-embedded tissues. In the brain, a light-microscopic study demonstrated strong immunoreactivity in neuronal somata and dendrites and weak immunoreactivity in nuclei. The densely stained regions included cerebral cortex, hippocampal formation, striatum, substantia nigra, and cerebellar cortex. In substantia nigra, neurites were stained, but not neuronal somata. Electron microscopy revealed that the immunoreactive product was highly concentrated at the postsynaptic densities. In addition to neurons, weak immunoreactivity was also demonstrated in glial cells, such as astrocytes and ependymal cells of ventricles and epithelial cells of choroid plexus. In other tissues, strong immunoreactivity was observed in the islet of pancreas and moderate immunoreactivity in skeletal muscle and kidney tubules. Immunoreactivity was demonstrated in all of the tissues tested. The results suggest that CaM kinase II is widely distributed in the tissues. 相似文献
142.
Respiration-dependent proton and sodium flows in a psychrophilicbacterium, Vibrio sp. strain ABE-1, were examined. At alkalinepH, this bacterium grew without being affected by a proton conductor,carbonylcyanide m-chlorophenylhydrazone (CCCP). O2-pulse intoanaerobic cell suspensions prepared with Na$-free buffers inducedtransient alkalization in the presence of CCCP and acidificationat pH 8.5 and 6.5, respectively. However, using cells preparedwith Na$-containing buffer, the transient pH changes of thecell suspension could be simultanously detected at both pHs.Several inhibitory experiments suggested that the acidificationand alkalization should be attributed to a respiration-dependentprimary H$ pump and Na$ pump, respectively, and that the latterwas similar to that first reported in a marine bacterium, Vibrioalginolyticus. This Na$ pump may have supported the CCCP-resistantgrowth at alkaline pH. The H$ and Na$ pumps operated very actively at low temperatures,such as 5?C, and should markedly help sustain bacterial growthat low temperatures. (Received May 30, 1987; Accepted November 13, 1987) 相似文献
143.
Shinji Takai Nariaki Fukunaga Kei Kamisawa Yumiko Imai Yukako Sasaki Shiro Tsubaki 《Microbiology and immunology》1996,40(8):591-594
We recently reported that there are two different virulence-associated antigens correlated with virulence levels in Rhodococcus equi isolates from AIDS patients: virulent R. equi that kills mice with 106 cells expresses 15- to 17-kDa antigens and intermediately virulent R. equi that kills mice with 107 cells expresses a 20-kDa antigen. Environmental parameters were evaluated for their effects on the expression of these virulence-associated antigens in virulent R. equi strains by immunoblotting using monoclonal antibodies in this study. Expression of these two virulence-associated antigens of R. equi was regulated by pH and temperature; the antigens were produced maximally when the isolates were grown at 38 C and pH 6.5, but were not produced when grown at 38 C and pH 8, nor at temperatures below 30 C. The 20-kDa antigen was found to be located on the cell surface, as were the 15- to 17-kDa antigens, and showed susceptibility to proteolysis by trypsin. These results indicate that expression of the virulence-associated antigens of R. equi is dependent on the environmental conditions. 相似文献
144.
The purpose of this study was to examine whether stretching training altered the viscoelastic properties of human tendon structures in vivo. Eight men performed the stretching training for 3 wk. Before and after the stretching training, the elongation of the tendon and aponeurosis of medial gastrocnemius muscle was directly measured by ultrasonography while the subjects performed ramp isometric plantar flexion up to the voluntary maximum, followed by a ramp relaxation. The relationship between the estimated muscle force (Fm) and tendon elongation (L) during the ascending phase was fitted to a linear regression, the slope of which was defined as stiffness of tendon structures. The percentage of the area within the Fm-L loop to the area beneath the curve during ascending phase was calculated as an index representing hysteresis. To assess the flexibility, the passive torque of the plantar flexor muscles was measured during the passive stretch from 0 degrees (anatomic position) to 25 degrees of dorsiflexion with a constant velocity of 5 degrees/s. The slope of the linear portion of the passive torque-angle curve during stretching was defined as flexibility index. Flexibility index decreased significantly after stretching training (-13.4 +/- 4.6%). On the other hand, the stretching training produced no significant change in stiffness but significantly decreased hysteresis from 19.9 +/- 11.7 to 12.5 +/- 9.5%. The present results suggested that stretching training affected the viscosity of tendon structures but not the elasticity. 相似文献
145.
Tsukasa Mizuhara Shinya Oishi Hiroaki Ohno Kazuya Shimura Masao Matsuoka Nobutaka Fujii 《Bioorganic & medicinal chemistry》2012,20(21):6434-6441
3,4-Dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine (PD 404182) is an antiretroviral agent with submicromolar inhibitory activity against human immunodeficiency virus-1 (HIV-1) and HIV-2 infection. In the current study, the structure–activity relationships of accessory groups at the 3- and 9-positions of pyrimido[1,2-c][1,3]benzothiazin-6-imine were investigated for the development of more potent anti-HIV agents. Several different derivatives containing a 9-aryl group were designed and synthesized using Suzuki–Miyaura cross-coupling and Ullmann coupling reactions. Modification of the m-methoxyphenyl or benzo[d][1,3]dioxol-5-yl group resulted in improved anti-HIV activity. In addition, the 2,4-diazaspiro[5.5]undec-2-ene-fused benzo[e][1,3]thiazine derivatives were designed and tested for their anti-HIV activities. The most potent 9-(benzo[d][1,3]dioxol-5-yl) derivative was two–threefold more effective against several strains of HIV-1 and HIV-2 than the parent compound, PD 404182. 相似文献
146.
The solvent effects of cyclopentyl methyl ether (CPME) on the reaction rates and enzyme enantioselectivity in the enantioselective transesterifications of racemic 6-methyl-5-hepten-2-ol (racemic sulcatol: SUL) and racemic 2,2-dimethyl-1,3-dioxolane-4-methanol (racemic solketal: SOL) with a series of enol esters catalyzed by Pseudomonas cepacia lipase co-lyophilized with cyclodextrins (-, -, -, partially methylated -,and 2,3,6-tri-O-methyl--cyclodextrin: CyD; CyD; CyD; Me1.78 CyD; Me3CyD) were investigated and compared with those in diisopropyl ether (IPE). In the case of SUL, enzyme activities of the co-lyophilizate with Me1.78 CyD in CPME were lower than those in IPE with every acyl source, however, the absolute enantiopreference was shown in the transesterification with vinyl butyrate (VBR) in IPME. When the substrates were SOL and VBR, the enzyme activities in CPME were greatly enhanced as high as 1.6–9.8-fold, while the enantioselectivities in CPME were comparable to those in IPE.Revisions requested 16 December 2004; Revisions received 17 January 2005 相似文献
147.
Shime H Yabu M Akazawa T Kodama K Matsumoto M Seya T Inoue N 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(11):7175-7183
148.
Deformation of the Outer Hair Cells and the Accumulation of Caveolin-2 in Connexin 26 Deficient Mice
Takashi Anzai Ichiro Fukunaga Kaori Hatakeyama Ayumi Fujimoto Kazuma Kobayashi Atena Nishikawa Toru Aoki Tetsuo Noda Osamu Minowa Katsuhisa Ikeda Kazusaku Kamiya 《PloS one》2015,10(10)
BackgroundMutations in GJB2, which encodes connexin 26 (Cx26), a cochlear gap junction protein, represent a major cause of pre-lingual, non-syndromic deafness. The degeneration of the organ of Corti observed in Cx26 mutant—associated deafness is thought to be a secondary pathology of hearing loss. Here we focused on abnormal development of the organ of Corti followed by degeneration including outer hair cell (OHC) loss.MethodsWe investigated the crucial factors involved in late-onset degeneration and loss of OHC by ultrastructural observation, immunohistochemistry and protein analysis in our Cx26-deficient mice (Cx26f/fP0Cre).ResultsIn ultrastructural observations of Cx26f/fP0Cre mice, OHCs changed shape irregularly, and several folds or notches were observed in the plasma membrane. Furthermore, the mutant OHCs had a flat surface compared with the characteristic wavy surface structure of OHCs of normal mice. Protein analysis revealed an increased protein level of caveolin-2 (CAV2) in Cx26f/fP0Cre mouse cochlea. In immunohistochemistry, a remarkable accumulation of CAV2 was observed in Cx26f/fP0Cre mice. In particular, this accumulation of CAV2 was mainly observed around OHCs, and furthermore this accumulation was observed around the shrunken site of OHCs with an abnormal hourglass-like shape.ConclusionsThe deformation of OHCs and the accumulation of CAV2 in the organ of Corti may play a crucial role in the progression of, or secondary OHC loss in, GJB2-associated deafness. Investigation of these molecular pathways, including those involving CAV2, may contribute to the elucidation of a new pathogenic mechanism of GJB2-associated deafness and identify effective targets for new therapies. 相似文献
149.
Syntheses and biological evaluation of novel quinuclidine derivatives as squalene synthase inhibitors 总被引:2,自引:0,他引:2
Ishihara T Kakuta H Moritani H Ugawa T Sakamoto S Tsukamoto S Yanagisawa I 《Bioorganic & medicinal chemistry》2003,11(11):2403-2414
Squalene synthase (E.C. 2.5.1.21) catalyses the reductive dimerization of two molecules of farnesyl diphosphate to form squalene and is involved in the first committed step in cholesterol biosynthesis. Inhibition of this enzyme is therefore an attractive target for hypocholesterolemic strategies. A series of quinuclidine derivatives incorporating a tricyclic system was synthesized and evaluated for their ability to inhibit squalene synthase in vitro. A 9H-fluorene moiety was found to be optimal as the tricyclic system for potent inhibitory activity. Improved activity can be achieved with a conformationally constrained three-atom linkage connecting the tricyclic system with the quinuclidine nucleus. Among these compounds, (Z)-3-[2-(9H-fluoren-2-yloxy)ethylidene]-quinuclidine hydrochloride 31 was found to be a potent inhibitor of squalene synthase derived from hamster liver and human hepatoma cells with IC(50) values of 76 and 48 nM, respectively. Oral dosing of compound 31 demonstrated effective reduction of plasma non-HDL cholesterol levels in hamsters. 相似文献
150.
Haruka Handa Ari Hashimoto Shigeru Hashimoto Hirokazu Sugino Tsukasa Oikawa Hisataka Sabe 《Cell communication and signaling : CCS》2018,16(1):94