全文获取类型
收费全文 | 2650篇 |
免费 | 174篇 |
出版年
2021年 | 18篇 |
2018年 | 15篇 |
2017年 | 20篇 |
2016年 | 40篇 |
2015年 | 54篇 |
2014年 | 71篇 |
2013年 | 164篇 |
2012年 | 145篇 |
2011年 | 143篇 |
2010年 | 79篇 |
2009年 | 71篇 |
2008年 | 124篇 |
2007年 | 137篇 |
2006年 | 134篇 |
2005年 | 132篇 |
2004年 | 144篇 |
2003年 | 146篇 |
2002年 | 188篇 |
2001年 | 79篇 |
2000年 | 74篇 |
1999年 | 77篇 |
1998年 | 25篇 |
1997年 | 28篇 |
1996年 | 29篇 |
1995年 | 16篇 |
1994年 | 21篇 |
1993年 | 28篇 |
1992年 | 58篇 |
1991年 | 28篇 |
1990年 | 35篇 |
1989年 | 37篇 |
1988年 | 34篇 |
1987年 | 27篇 |
1986年 | 36篇 |
1985年 | 32篇 |
1984年 | 24篇 |
1983年 | 26篇 |
1982年 | 15篇 |
1981年 | 18篇 |
1980年 | 24篇 |
1979年 | 13篇 |
1978年 | 16篇 |
1976年 | 16篇 |
1975年 | 19篇 |
1974年 | 15篇 |
1972年 | 13篇 |
1971年 | 14篇 |
1970年 | 16篇 |
1969年 | 12篇 |
1966年 | 14篇 |
排序方式: 共有2824条查询结果,搜索用时 250 毫秒
1.
Hisao Tsukamoto Yoshihiro Kubo David L. Farrens Mitsumasa Koyanagi Akihisa Terakita Yuji Furutani 《The Journal of biological chemistry》2015,290(45):27176-27187
Melanopsins play a key role in non-visual photoreception in mammals. Their close phylogenetic relationship to the photopigments in invertebrate visual cells suggests they have evolved to acquire molecular characteristics that are more suited for their non-visual functions. Here we set out to identify such characteristics by comparing the molecular properties of mammalian melanopsin to those of invertebrate melanopsin and visual pigment. Our data show that the Schiff base linking the chromophore retinal to the protein is more susceptive to spontaneous cleavage in mammalian melanopsins. We also find this stability is highly diversified between mammalian species, being particularly unstable for human melanopsin. Through mutagenesis analyses, we find that this diversified stability is mainly due to parallel amino acid substitutions in extracellular regions. We propose that the different stability of the retinal attachment in melanopsins may contribute to functional tuning of non-visual photoreception in mammals. 相似文献
2.
K. Yoshikawa 《Journal of biological physics》2002,28(4):701-712
The mechanism of the self-regulation of gene expression in living cells is generally explained by considering complicated networks of key-lock relationships, and in fact there is a large body of evidence on a hugenumber of key-lock relationships. However, in the present article we stress that with the network hypothesis alone it is impossible to fully explain the mechanism of self-regulation in life. Recently, it has been established that individual giant DNA molecules, larger than several tens of kilo base pairs, undergo a large discrete transition in their higher-order structure. It has become clear that nonspecific weak interactions with various chemicals, suchas polyamines, small salts, ATP and RNA, cause on/off switching in the higher-order structure of DNA. Thus, the field parameters of the cellular environment should play important roles in the mechanism of self-regulation, in addition to networks of key and locks. This conformational transition induced by field parameters may be related to rigid on/off regulation, whereas key-lock relationships may be involved in a more flexible control of gene expression. 相似文献
3.
Yuichi Mori Yoshitaka Miura Yutaka Oiso Seo Hisao Kozaki Takazumi 《Human genetics》1995,96(4):481-482
The human thyroxine-binding globulin (TBG) gene has been localized to X chromosome (Xq22.2) by in situ hybridization using a biotinylated gDNA probe. This is consistent with previous mapping of the TBG gene to chromosome Xq21-q22. 相似文献
4.
5.
T Yoshikawa H Terayama 《Comparative biochemistry and physiology. A, Comparative physiology》1984,77(1):39-44
Pancreatectomy as well as thyroparathyroidectomy resulted in the quick disappearance of a serum factor (stimulating cathepsin D release from lysosomes in vitro) from the rat or mouse blood. Extirpation of other organs such as duodenum, stomach, spleen, kidney, submaxillary gland, testis, adrenal gland or hypophysis, showed no effect on the serum factor level. Glucagon (but not insulin or thyroxine) given to the pancreatectomized animals restored the serum factor level in a dose-dependent manner. The serum factor-like activity was detected only in the parathyroids (but not thyroid), and the release of activity from parathyroid-slices was stimulated by glucagon, suggesting that the parathyroid may produce and/or secrete the serum factor under the influence of glucagon. 相似文献
6.
Growth of cell-free subacute sclerosing panencephalitis (SSPE) virus was compared with that of measles virus in three human neural cell lines; neuroblastoma, oligodendroglioma, and glioblastoma. The Edmonston strain of measles virus replicated in these neural cells as efficiently as in Vero cells. In contrast, the growth of the Mantooth strain of SSPE virus was suppressed moderately in neuroblastoma cells and markedly in oligodendroglioma and glioblastoma cells in spite of the induction of apparent cytopathic effects in these cells. Virus adsorption, defective interfering particles, interferon, and temperature sensitivity were not responsible for this low yield of SSPE virus in neural cell lines. Synthesis of viral proteins of SSPE virus was slower than that of measles virus in oligodendroglioma and glioblastoma cells. These results suggest that the slow rate of synthesis of viral proteins may be relevant to the low yield of SSPE virus in neural cells. 相似文献
7.
An endopeptidase was solubilized and highly purified from the synaptosomal membrane fraction of guinea pig brain, and its specificity of action on various neuropeptides was investigated. It hydrolyzed specifically the Pro10-Tyr11 bond of neurotensin and showed a marked specificity toward Pro-X bonds present in the interior parts of various neuropeptides and related peptides. No cleavage, however, was observed at the first and second peptide bonds from the NH2-termini or from the COOH-termini of the peptides examined, suggesting that the enzyme requires both NH2- and COOH-terminal extentions of at least 3 residues from the scissile bond for its action. In addition, a limited number of other peptide bonds were cleaved, indicating that the enzyme is not strictly specific to Pro-X bonds. These results suggest the possible implication of this enzyme in the specific degradation of neurotensin and other peptide neurotransmitters in the synaptic cleft. 相似文献
8.
The fine structure of the trophozoite and cyst of Entamoeba histolytica from the stool of a patient was compared using the freeze-fracture method. The intramembranous particles (IMP's) were heterogeneously distributed on the plasma membrane of the trophozoite and their density was 1139 +/- 105/micron 2 on the P face. Particle-rich depressions and linear particle arrays, reported by other investigators on cultured trophozoites, were also observed on the P face while on the E face such special particle arrangement was not recognized. Particle-free, small protrusions were frequently observed on the P face of the trophozoite membrane. The existence of these protrusions is a new finding. In the cyst, the IMP's were also distributed heterogeneously on both the P and E faces of the plasma membrane. The density of the IMP's, however, was much lower than in the trophozoite: 6 +/- 2/micron 2 on the P face and averaging less than 1/micron 2 on the E face. In freeze-fracture images, the plasma membrane of the cyst showed a variety of configurations from smooth to uneven or ridged surfaces. These morphological alterations of the plasma membrane may be attributed to the aging of the cyst. The thick wall of the cyst had a filamentous tri- or tetra-lamellar structure. The cytoplasm of the cyst was similar in structure to that of the trophozoite and the diameter of the nuclear pores was equal in both trophozoites and cysts. 相似文献
9.
Yoshiaki Suzuki Hisao Yamamura Susumu Ohya Yuji Imaizumi 《Biochemical and biophysical research communications》2013,430(3):1169-1174
Caveolin family is supposed to be essential molecules for the formation of not only caveola structure on cell membrane but also functional molecular complexes in them with direct and/or indirect interaction with other membrane and/or submembrane associated proteins. The direct coupling of caveolin-1 (cav1) with large conductance Ca2+-activated K+ channel, KCa1.1 has been established in several types of cells and in expression system as well. The possible interaction of caveolin-3 (cav3), which shows expression in some differential tissues from cav1, with KCa1.1 remains to be determined. In the present study, the density of KCa1.1 current expressed in HEK293 cells was significantly reduced by the co-expression of cav3, as well as cav1. The co-localization and direct interaction of GFP- or CFP-labeled cav3 (GFP/CFP-cav3) with YFP- or mCherry-labeled KCa1.1 (KCa1.1-YFP/mCherry) were clearly demonstrated by single molecular image analyses using total internal reflection fluorescence (TIRF) microscopy and fluorescence resonance energy transfer (FRET) analyses with acceptor photobleaching method. The deletion of suggested cav1-binding motif in C terminus region of KCa1.1 (KCa1.1ΔCB-YFP) resulted in the marked decrease in cell surface expression, co-localization and FRET efficiency with CFP-cav3 and CFP-cav1. The FLAG-KCa1.1 co-immunoprecipitation with GFP-cav3 or GFP-cav1 also supported their direct molecular interaction. These results strongly suggest that cav3 possesses direct interaction with KCa1.1, presumably at the same domain for cav1 binding. This interaction regulates KCa1.1 expression to cell surface and the formation of functional molecular complex in caveolae in living cells. 相似文献
10.
M Hayami M Ito Y Yoshikawa K Yamanouchi 《Japanese journal of medical science & biology》1976,29(1):11-24
Temporal appearance of cellular cytotoxicity and humoral activities including blocking and arming activities during the entire course of Rous sarcoma development in Japanese quails was examined by microcytotoxicity assay with comparison of animals bearing regressing tumors induced by a moderate dose of virus (regressors) and animals bearing growing tumors induced by a large dose of virus (progressors). Cellular cytotoxicity of the spleen cells in regressors was detected in a biphasic pattern; the first phase being observed as early as 3-5 days post inoculation (p.i.), followed by an eclipse period between 7-10 days p.i. which was the time of active tumor growth, and the second phase occurring after 12 days p.i. when the tumor had attained the maximum size. In progressors, only the first phase was observed. Instead, a stimulatory effect of the spleen cells on growth of target cells was noticed. Arming activity which confers cytotoxic activity on the normal spleen cells was demonstrated in the sera of regressors in the similar biphasic pattern as the cellular cytotoxicity; the early activity being present at 3 days p.i., and the late one after 19 days p.i. The former was detected by pre-incubation of serum with effector cells in microcytotoxicity assay and the latter by pre-incubation with target cells. In progressors, only the early arming activity which reacts with effector cells was demonstrated. Blocking activity which abrogates cellular cytotoxicity was demonstrated in both regressors and progressors but in different patterns of appearance, that is, blocking activity in regressors was only transiently demonstrated only by pre-incubation with effector cells at the time of maximum tumor growth, while the activity in progressors seemed to persist after the tumor reached the maximum size. Since the earlier activity was found to be effective at effector cell level, and the later one at both effector and target cell levels, participation of blocking factors of different types in progressors was also suggested. 相似文献