全文获取类型
收费全文 | 394篇 |
免费 | 22篇 |
国内免费 | 2篇 |
出版年
2021年 | 5篇 |
2020年 | 3篇 |
2019年 | 6篇 |
2018年 | 5篇 |
2017年 | 3篇 |
2016年 | 4篇 |
2015年 | 11篇 |
2014年 | 16篇 |
2013年 | 36篇 |
2012年 | 29篇 |
2011年 | 29篇 |
2010年 | 12篇 |
2009年 | 4篇 |
2008年 | 18篇 |
2007年 | 18篇 |
2006年 | 13篇 |
2005年 | 20篇 |
2004年 | 14篇 |
2003年 | 18篇 |
2002年 | 21篇 |
2001年 | 7篇 |
2000年 | 5篇 |
1999年 | 5篇 |
1998年 | 10篇 |
1996年 | 7篇 |
1995年 | 6篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1992年 | 7篇 |
1991年 | 7篇 |
1990年 | 4篇 |
1989年 | 7篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1985年 | 3篇 |
1984年 | 8篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 6篇 |
1980年 | 6篇 |
1979年 | 4篇 |
1977年 | 1篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1974年 | 5篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1971年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有418条查询结果,搜索用时 250 毫秒
101.
102.
Microtubules are cylindrical organelles that play critical roles in cell division. Their subunit protein, tubulin, is a target for various antitumor drugs. Tubulin exists as various forms, known as isotypes. In most normal cells, tubulin occurs only in the cytosol and not in the nucleus. However, we have recently reported the finding of the beta(II) isotype of tubulin in the nuclei of cultured rat kidney mesangial cells. Mesangial cells, unlike most normal cell lines, have the ability to proliferate rapidly in culture. In efforts to determine whether nuclear beta(II)-tubulin occurred in other cell lines, we examined the distribution of the beta(I), beta(II), and beta(IV) mammalian tubulin isotypes in a variety of normal and cancer human cell lines by immunofluorescence microscopy. We have found that, in the normal cell lines, all three isotypes are present only in the cytoplasm. However, the beta(II) isotype of tubulin is located not only in the cytoplasm, but also in the nuclei of the following cell lines: LNCaP prostate carcinoma, MCF-7, MDA-MB-231, MDA-MB-435, and Calc18 breast carcinoma, C6 and T98G glioma, and HeLa cells. In contrast, the beta(I) and beta(IV) isotypes, which are also synthesized in cancer cells, are not localized to the nucleus but are restricted to the cytoplasm. We have also seen beta(II) in breast cancer excisions. In most of these cells, beta(II) appears to be concentrated in the nucleoli. These results suggest that transformation may lead to localization of beta(II)-tubulin in cell nuclei, serving an as yet unknown function, and that nuclear beta(II) may be a useful marker for detection of tumor cells. 相似文献
103.
Bcl-2 family member Bfl-1/A1 sequesters truncated bid to inhibit is collaboration with pro-apoptotic Bak or Bax 总被引:11,自引:0,他引:11
Werner AB de Vries E Tait SW Bontjer I Borst J 《The Journal of biological chemistry》2002,277(25):22781-22788
Following caspase-8 mediated cleavage, a carboxyl-terminal fragment of the BH3 domain-only Bcl-2 family member Bid transmits the apoptotic signal from death receptors to mitochondria. In a screen for possible regulators of Bid, we defined Bfl-1/A1 as a potent Bid interacting protein. Bfl-1 is an anti-apoptotic Bcl-2 family member, whose preferential expression in hematopoietic cells and endothelium is controlled by inflammatory stimuli. Its mechanism of action is unknown. We find that Bfl-1 associates with both full-length Bid and truncated (t)Bid, via the Bid BH3 domain. Cellular expression of Bfl-1 confers protection against CD95- and Trail receptor-induced cytochrome c release. In vitro assays, using purified mitochondria and recombinant proteins, demonstrate that Bfl-1 binds full-length Bid, but does not interfere with its processing by caspase-8, or with its mitochondrial association. Confocal microscopy supports that Bfl-1, which at least in part constitutively localizes to mitochondria, does not impede tBid translocation. However, Bfl-1 remains tightly and selectively bound to tBid and blocks collaboration between tBid and Bax or Bak in the plane of the mitochondrial membrane, thereby preventing mitochondrial apoptotic activation. Lack of demonstrable interaction between Bfl-1 and Bak or Bax in the mitochondrial membrane suggests that Bfl-1 generally prevents the formation of a pro-apoptotic complex by sequestering BH3 domain-only proteins. 相似文献
104.
We studied the production of interleukin (IL)-11 and IL-8, two cytokines known to affect erythropoiesis, in polycythemia vera (PV). In vivo, IL-11 was detected more frequently in serum and bone marrow (BM) plasma of PV patients than in controls (healthy donors and patients with idiopathic erythrocytosis (IE)). In addition, serum IL-11 levels of PV patients were higher than those of controls. IL-8 was elevated in serum of both PV and IE patients (respective median levels: 38.6 and 242pg/ml, vs 4.4pg/ml for healthy donors). BM plasma IL-8 levels of PV patients (508pg/ml) were significantly higher than those of IE patients (120pg/ml). In vitro, bone marrow (BM) stromal cells (BMSC) of PV patients produced significantly more IL-11 (x6.4) and IL-8 (x8.3) than BMSC of healthy donors or IE patients. In conclusion, both IL-11 and IL-8 are overproduced in PV, apparently by BMSC; IL-8 is also overproduced in IE, by cells other than BMSC. 相似文献
105.
Jean-Pierre Souchard Marie-Aline Barbacanne Emmanuel Margeat Arlette Maret Fran oise Nepveu Jean-Fran ois Arnal 《Free radical research》1998,29(5):441-449
Objective and Methods Endothelium produces oxygen-derived free radicals which play a major role in vessel wall physiology and pathology. Whereas NO· production from endothelium has been extensively characterized, little is known about endothelium-derived O-·2. In the present study, we determined the O-·2 production of bovine aortic endothelial cells (BAEC) using the spin trap 5,5-dimethyl-1 pyrroline-N-oxide (DMPO) and electron spin resonance (ESR) spectroscopy.
Results An ESR adduct DMPO-OH detected in the supernatant of BAEC after stimulation with the calcium ionophore A23187 originated from the trapping of extracellular O-·2, because coincubation with superoxide dismutase (30 U/ml) completely suppressed the ESR signal, whereas catalase (2000 U/ml) had no effect. A23187 stimulated extracellular O-·2 production in a time- and dose-dependent manner. The coenzymes NADH and NADPH both increased the ESR signal, whereas a flavin antagonist, diphenylene iodonium, abolished the ESR signal. Phorbol myristate acetate potentiated, whereas bisindolylmaleimide I inhibited the A23187-stimulated O-·2 production, suggesting the involvement of protein kinase C. These signals were not altered L-NAME, a NO-synthase inhibitor, suggesting that the endogenous production of NO· did not alter O-·2 production. Finally, the amount of O-·2 generated by A23187-stimulated post-confluent BAEC was one order of magnitude higher than that evoked by rat aortic smooth muscle cells stimulated under the same conditions. 相似文献
Results An ESR adduct DMPO-OH detected in the supernatant of BAEC after stimulation with the calcium ionophore A23187 originated from the trapping of extracellular O-·2, because coincubation with superoxide dismutase (30 U/ml) completely suppressed the ESR signal, whereas catalase (2000 U/ml) had no effect. A23187 stimulated extracellular O-·2 production in a time- and dose-dependent manner. The coenzymes NADH and NADPH both increased the ESR signal, whereas a flavin antagonist, diphenylene iodonium, abolished the ESR signal. Phorbol myristate acetate potentiated, whereas bisindolylmaleimide I inhibited the A23187-stimulated O-·2 production, suggesting the involvement of protein kinase C. These signals were not altered L-NAME, a NO-synthase inhibitor, suggesting that the endogenous production of NO· did not alter O-·2 production. Finally, the amount of O-·2 generated by A23187-stimulated post-confluent BAEC was one order of magnitude higher than that evoked by rat aortic smooth muscle cells stimulated under the same conditions. 相似文献
106.
Arlette Fellous Veena Prasad Renée Ohayon Mary Ann Jordan Richard F. Ludueña 《Journal of Protein Chemistry》1994,13(4):381-391
Microtubule-associated proteins (MAPs) can promote microtubule assemblyin vitro. One of these MAPs (MAP2) consists of a short promoter domain which binds to the microtubule and promotes assembly and a long projection domain which projects out from the microtubule and may interact wth other cytoskeletal elements. We have previously shown that MAP2 and another MAP, tau, differ in their interactions with tubulin in that tau, but not MAP2, promotes extensive aggregation of tubulin into spiral clusters in the presence of vinblastine and that microtubules formed with MAP2 are more resistant than those formed with tau to the antimitotic drug maytansine [Luduena, R. F.,et al. (1984),J. Biol. Chem.
259, 12890–12898; Fellous, A.,et al. (1985),Cancer Res.
45, 5004–5010]. Here we have used chymotryptic digestion to remove the projection domain of MAP2 and examined the interaction of the digested MAP2 (ctMAP2) with tubulin in the presence of vinblastine and maytansine. We have found that ctMAP2 behaves very much like tau, but not like undigested MAP2, in the presence of vinblastine, in that ctMAP2 causes tubulin to polymerize into large clusters of spirals. In contrast, microtubule assembly in the presence of ctMAP2 is much more resistant to maytansine inhibition than is assembly in the presence of tau or undigested MAP2. Our results suggest that the projection domain of MAP2 may play a role in the interaction of tubulin with MAP2 during microtubule assembly.Abbreviations MAPs
microtubule-associated proteins
- ctMAP2
MAP2 digested with-chymotrypsin
- nMAP2
untreated MAP2
- PMSF
phenylmethylsulfonyl fluoride
- GMPCPP
guanosine-5-(,-methylene)triphosphate 相似文献
107.
Margaret E. Buckingham Arlette Cohen François Gros 《Journal of molecular biology》1976,103(3):611-626
Total poly(A)-containing RNA in different polysomal and supernatant cytoplasmic fractions was analysed after pulse-labelling in dividing myoblasts and fused myotubes. In particular, the peak of 26 S RNA (putative messenger for the large subunit of myosin) is located in a light region of the gradient coinciding with the monosome-trisome fractions prior to fusion, and is found in the heavy polysomes only after fusion. These heavy polysomes are free (i.e. not membrane bound). Treatment of the light part of the polysome gradient with EDTA shows that the 26 S RNA found here does not exist as part of a polysomal complex, but is present as a ribonucleoprotein particle cosedimenting in this region. Previous experiments had indicated that in actively dividing myoblasts 26 S RNA has a relatively short half-life but that it becomes “stable” after the cessation of mitosis just prior to fusion. RNA chase experiments performed in the present study show that the “short-lived” 26 S RNA from dividing myoblasts, which is present as a ribonucleoprotein particle, does not enter the heavy polysomes. In contrast, the more stable 26 S RNA also initially present as a ribonucleoprotein, just prior to and in the early stages of fusion, can be shown by chase experiments to enter the heavy polysomes later in fusion. Hence accumulation of 26 S RNA seems to precede its activation as a messenger. 相似文献
108.
Sergio Salardi Lucia Tosi Arlette Garnier-Suillerot Claudio Toniolo Gian Maria Bonora Fernando Marchiori 《Biopolymers》1982,21(6):1229-1243
The interaction of Cu(II) with the protamine clupeine YII (containing proline at the N-terminal) and with four peptides (H-Ala-Arg-OMe, H-Ala-Arg2-OMe, H-Pro-Arg-OMe, and H-Arg4-Tyr) has been studied by means of absorption, CD, and pH neasurements. The first two peptides mimic clupeine YI and Z N-terminals; the third, the clupeine YII N-terminal. At 1:1 molar ratio, clupeine YII yields two complexes: the first (I), at pH 6.6, through coordination via the N-terminal and the contiguous peptide nitrogen forming a five-membered chelate; the second (II), at pH 8.5, through the occupancy of the other two corners of the coordination square by amino nitrogens of the lateral chains. These complexes are strictly analogous and occur at the same pH as those formed with clupeine Z. Under the same conditions, all the peptides yield complex I in the first step, although the pH at which this complex is fully defined depends on the number of residues in the chain. It is 8.5 for dipeptides, decreases to 6.5 by the addition of a third residue to the chain, and remains constant when the number of residues is three or more. The amino nitrogens of lateral chains are unable to coordinate to the metal in a second step unless one additional peptide bond lies between the N-terminal residue and that containing the lateral chain bound to the metal. Thus, H-Ala-Arg-OMe and H-Pro-Arg-OMe form hydroxyl complexes in a second step (pH 11), by deprotonation of one of the water molecules coordinated to the metal; one of the lateral chains of H-Ala-Arg2-OMe is able to coordinate in a second step (pH 8.5), but it is only with H-Arg4-Tyr that a second complex (II) is obtained in which two amino nitrogens of lateral chains supersede the oxygens of water molecules in I, at pH 8.5. 相似文献
109.
The purpose of this work was to determine the conformation adopted in solution by adozelesin, carzelesin, and their derivatives obtained under basic or acidic conditions. Circular dichroism in the 270–330 nm wavelengths region was studied. In solution adozelesin can adopt two different conformations: a left-handed one which is thermodynamically favoured at low temperature and is mainly present at room temperature, and a right-handed one which is observed either at high temperature or at room temperature in the presence of DNA. This was ascertained by the presence of circular dichroism signals of the couplet type. The active form of carzelesin, i.e., U-76074, also exhibited a left-handed conformation in solution. Carzelesin and the derivatives obtained under acidic conditions that lack the cyclopropyl ring, and cyclopropylpyrroloindole, obtained under basic conditions, cannot adopt such a conformation. Chirality 8:585–589, 1996. © 1997 Wiley-Liss, Inc. 相似文献
110.
Alteration of the Leptin Network in Late Morbid Obesity Induced in Mice by Brain Infection with Canine Distemper Virus
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)