全文获取类型
收费全文 | 2398篇 |
免费 | 140篇 |
国内免费 | 3篇 |
出版年
2023年 | 6篇 |
2022年 | 12篇 |
2021年 | 21篇 |
2020年 | 11篇 |
2019年 | 23篇 |
2018年 | 24篇 |
2017年 | 26篇 |
2016年 | 30篇 |
2015年 | 69篇 |
2014年 | 84篇 |
2013年 | 160篇 |
2012年 | 143篇 |
2011年 | 140篇 |
2010年 | 83篇 |
2009年 | 95篇 |
2008年 | 172篇 |
2007年 | 156篇 |
2006年 | 127篇 |
2005年 | 157篇 |
2004年 | 138篇 |
2003年 | 164篇 |
2002年 | 182篇 |
2001年 | 32篇 |
2000年 | 32篇 |
1999年 | 33篇 |
1998年 | 44篇 |
1997年 | 28篇 |
1996年 | 18篇 |
1995年 | 25篇 |
1994年 | 24篇 |
1993年 | 20篇 |
1992年 | 34篇 |
1991年 | 16篇 |
1990年 | 20篇 |
1989年 | 16篇 |
1988年 | 18篇 |
1987年 | 19篇 |
1986年 | 12篇 |
1985年 | 11篇 |
1984年 | 22篇 |
1983年 | 6篇 |
1982年 | 12篇 |
1981年 | 9篇 |
1980年 | 15篇 |
1979年 | 8篇 |
1978年 | 6篇 |
1977年 | 7篇 |
1976年 | 5篇 |
1975年 | 7篇 |
1973年 | 4篇 |
排序方式: 共有2541条查询结果,搜索用时 15 毫秒
991.
Rapid G0/1 transition and cell cycle progression in CD8+ T cells compared to CD4+ T cells following in vitro stimulation
下载免费PDF全文
![点击此处可从《Microbiology and immunology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Takuya Mishima Shotaro Fukaya Shoko Toda Yoshiaki Ando Tsukasa Matsunaga Manabu Inobe 《Microbiology and immunology》2017,61(5):168-175
T‐cell population consists of two major subsets, CD4+ T cells and CD8+ T cells, which can be distinguished by the expression of CD4 or CD8 molecules, respectively. Although they play quite different roles in the immune system, many of their basic cellular processes such as proliferation following stimulation are presumably common. In this study, we have carefully analyzed time–course of G0/1 transition as well as cell cycle progression in the two subsets of quiescent T‐cell population following in vitro growth stimulation. We found that CD8+ T cells promote G0/1 transition more rapidly and drive their cell cycle progression faster compared to CD4+ T cells. In addition, expression of CD25 and effects of its blockade revealed that IL‐2 is implicated in the rapid progression, but not the earlier G0/1 transition, of CD8+ T cells. 相似文献
992.
993.
Yuki Nagaya Yoshiaki Kitamura Aya Shibata Masato Ikeda Yukihiro Akao Yukio Kitade 《Bioorganic & medicinal chemistry letters》2017,27(24):5454-5456
Chemically modified siRNAs containing 2-O-benzyl-1-deoxy-d-ribofuranose (RHOBn) in their 3′-overhang region were significantly more resistant towards serum nucleases than siRNAs possessing the natural nucleoside in this region. The knockdown efficacies and binding affinities of these modified siRNAs to the recombinant human Argonaute protein 2 (hAgo2) PAZ domain were comparable with that of siRNA with a thymidine dimer at the 3′-end. 相似文献
994.
Kiyoshi Suzuki Shinichi Kitamura Yoshiaki Sone Takao Itoh 《Journal of molecular histology》2003,34(11-12):535-544
The distribution of hemicelluloses and pectins in bamboo internodes was studied immunocytochemistrically at various stages of development. The ultra-structures of bamboo cell walls have been reported previously at various stages. The internodes were identically classified into three developmental phases: primary wall stage (phase I), unlignified secondary wall stage (phase II) and lignified wall stage (phase III), using the same bamboo culm. (1→,1→4)-β-Glucans were distributed in nearly all tissues in an actively elongating stage. Limited amounts of β-glucans were deposited in primary walls and the middle lamellae, but were limited to the phloem in secondary walls. This suggests that the function of β-glucans might be different in phloem vis-à-vis other tissues. Highly-substituted xylans were located in nearly all tissues of early phase I, but had disappeared in all tissues immediately prior to lignification. In contrast, low-branched xylan epitopes were present only in the protoxylem in phase I, but were present in all tissues immediately prior to lignification in phase II. In phase III, the epitopes were densely localized in lignified walls, suggesting that the substitution of xylans is closely related to maturation. Methyl-esterified (but not unesterified) pectins were present in all tissues of early phase I. Just before and after lignification, both types of pectins were concentrated in the phloem and protoxylem. Xyloglucans were largely distributed in the phloem and in lignified tissues, suggesting that they might be closely correlated with maturation. This represents the first account of the distribution of hemicelluloses and pectins at the tissue and ultrastructural level in bamboo internodes at various stages of development. 相似文献
995.
Dual regulation of mouse Delta(5)- and Delta(6)-desaturase gene expression by SREBP-1 and PPARalpha. 总被引:8,自引:0,他引:8
996.
997.
Yosuke Ando Nobutsune Ichihara Shigehito Takeshita Yoshiaki Saito Takeki Kikuchi Noboru Wakasugi 《Experimental Animals》2004,53(2):81-88
The cerebellar calcification (CC) rat is a new neurodegenerative mutant with severe Purkinje cell loss and symmetrical calcifications in the cerebellar cortex manifesting ataxia: lack of coordination in body movements. In the present study, histopathological features were examined in the Purkinje cell degeneration in postnatal homozygous suckling rats without clinical signs, which were genotyped by microsatellite markers. In addition, the calcified Purkinje cells were investigated ultrastructurally and elemental analysis was performed on the deposits. Body weight of the homozygous (cc/cc) rats was already slightly lower compared with the heterozygotes (cc/+) in the neonatal stage. The degeneration of the Purkinje cells in the cc/cc rats was recognized obviously in lobules VI, VII, VIII and IX from 14 days after birth, a few days before the appearance of the ataxic behavior. The Purkinje cells in the region along the fissure between the VIII and IX lobule areas were intensely positive for periodic acid-Schiff reaction specific to glycoconjugates, and in this region, calcium depositions were weakly positive for von Kossa's stain. Electron microscopy also revealed that the calcified Purkinje cells possessed numerous electron-dense bodies containing inclusions with cystic structures such as vesicles, mitochondria and lysosomes, and these bodies were mainly composed of calcium and phosphorous. These findings suggest abnormal storage of glycoconjugates might be a trigger of Purkinje cell degeneration and serves as a matrix for accumulation of calcium phosphate in the cerebellum of CC rats. 相似文献
998.
Imaizumi Yuji Ohi Yoshiaki Yamamura Hisao Morimura Kozo Muraki Katsuhiko 《Neurophysiology》2003,35(3-4):169-174
The contribution of the Ca2+-induced Ca2+ release (CICR) mechanism in excitation-contraction (E-C) coupling and the tightness of the coupling between Ca2+ influx and Ca2+ release are still controversial in smooth muscle cells (SMC). In SMC isolated from the guinea-pig vas deferens or urinary bladder, a depolarizing stimulus initially induced spot-like increases in the intracellular Ca2+ concentration ([Ca2+] i ), called “Ca2+ hot spots,” at several superficial areas in the cell. When a weak stimulus (a small or a short depolarizing step) was applied, only a few Ca2+ hot spots appeared transiently in the superficial area but did not spread into other regions, to trigger global [Ca2+] i rise. Such depolarization-evoked local Ca2+ transients were distinctive from spontaneous Ca2+ sparks, since the former were susceptible to Ca2+ blockers, ryanodine, and inhibitors of the Ca2+ pump in the sarcoplasmic reticulum (SR), suggesting pivotal roles of Ca2+ influx through voltage-dependent Ca2+ channels (VDCC) and Ca2+ release from the SR through ryanodine receptors (RyR) for the activation of Ca2+ spots. Frequently discharging Ca2+ spark sites (FDS) under resting conditions were located exactly in the same areas as Ca2+ hot spots evoked by depolarization, indicating the existence of distinct local junction sites for tight coupling between VDCC in the plasmalemma and RyR in the SR. Co-localization of clusters of RyR and large-conductance Ca2+-activated K+ (BK) channels was also suggested. The fast and tight coupling for CICR in these junctional sites was triggered also by an action potential, whereas a slower spread of Ca2+ wave to the whole-cell areas suggests the loose coupling in propagating CICR to other cell areas. It can therefore be postulated that CICR may occur in two steps upon depolarization; the initial CICR in distinct junctional sites shows tight coupling between Ca2+ influx and release, and the following CICR may propagate slow Ca2+ waves to other areas. Ryanodine receptors form a multiprotein complex with molecules such as calsequestrin, junctin, triadin, junctophilins, and FK506-binding proteins, which directly or indirectly regulate the RyR activity and the tight coupling. Moreover, an evoked Ca2+ spot may enhance Ca2+ uptake by neighboring mitochondria and their ATP production to increase energy supply to the Ca2+ pump of the SR in the microdomain. 相似文献
999.
Prolonged Gray Matter Disease without Demyelination Caused by Theiler's Murine Encephalomyelitis Virus with a Mutation in VP2 Puff B
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Ikuo Tsunoda Yoshiaki Wada Jane E. Libbey Thomas S. Cannon Frank G. Whitby Robert S. Fujinami 《Journal of virology》2001,75(16):7494-7505
Theiler's murine encephalomyelitis virus (TMEV) is divided into two subgroups based on neurovirulence. During the acute phase, DA virus infects cells in the gray matter of the central nervous system (CNS). Throughout the chronic phase, DA virus infects glial cells in the white matter, causing demyelinating disease. Although GDVII virus also infects neurons in the gray matter, infected mice developed a severe polioencephalomyelitis, and no virus is detected in the white matter or other areas in the CNS in rare survivors. Several sequence differences between the two viruses are located in VP2 puff B and VP1 loop II, which are located near each other, close to the proposed receptor binding site. We constructed a DA virus mutant, DApBL2M, which has the VP1 loop II of GDVII virus and a mutation at position 171 in VP2 puff B. While DApBL2M virus replicated less efficiently than DA virus during the acute phase, DApBL2M-induced acute polioencephalitis was comparable to that in DA virus infection. Interestingly, during the chronic phase, DApBL2M caused prolonged gray matter disease in the brain without white matter involvement in the spinal cord. This is opposite what is observed during wild-type DA virus infection. Our study is the first to demonstrate that conformational differences via interaction of VP2 puff B and VP1 loop II between GDVII and DA viruses can play an important role in making the transition of infection from the gray matter in the brain to the spinal cord white matter during TMEV infection. 相似文献
1000.
Masahiko Obayashi Takayoshi Kosugi Jun-ichi Yamazaki Yoshiaki Matsumoto Masamichi Fukuoka Mitsuo Matsumoto 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1999,726(1-2)
An optimized method for the determination of flecainide in serum is presented. Extraction using a solid-phase C18 column and chromatography on a stabilized fluorocarbon-bonded silica gel column effectively separate flecainide from an internal standard (a positional isomer of flecainide). The HPLC apparatus and conditions were as follows: analytical column, Fluofix 120N; sample solvent, 20 μl; column temperature, 40°C; detector, Shimadzu RF-5000 fluorescence spectrophotometer (excitation wavelength=300 nm, emission wavelength=370 nm); mobile phase, 0.06% phosphoric acid containing 0.1% tetra-n-butyl ammonium bromide–acetonitrile (75:25, v/v); flow-rate, 1.0 ml/min. The standard curves for flecainide were linear in the concentration range examined (10–2000 ng/ml). The regression equation was y=0.08+0.0078x (r=0.9998). The minimum detectable amount of flecainide was approximately 5 ng/ml. In the within-day study, the precision coefficients of variation were 2.66, 2.18, 2.54, 2.72, 2.88, 2.24, and 3.29% for the 10, 50, 100, 200, 500, 1000, and 1500 ng/ml standards, respectively. The absolute recovery rates of flecainide at each concentrations were 94–100%. The method described provides analytical sensitivity, specificity and reproducibility suitable for both biomedical research and therapeutic drug monitoring. 相似文献