全文获取类型
收费全文 | 2335篇 |
免费 | 168篇 |
国内免费 | 1篇 |
出版年
2023年 | 11篇 |
2022年 | 33篇 |
2021年 | 60篇 |
2020年 | 19篇 |
2019年 | 46篇 |
2018年 | 81篇 |
2017年 | 52篇 |
2016年 | 72篇 |
2015年 | 110篇 |
2014年 | 136篇 |
2013年 | 173篇 |
2012年 | 197篇 |
2011年 | 211篇 |
2010年 | 135篇 |
2009年 | 114篇 |
2008年 | 127篇 |
2007年 | 174篇 |
2006年 | 150篇 |
2005年 | 128篇 |
2004年 | 119篇 |
2003年 | 116篇 |
2002年 | 87篇 |
2001年 | 27篇 |
2000年 | 10篇 |
1999年 | 13篇 |
1998年 | 12篇 |
1997年 | 7篇 |
1996年 | 4篇 |
1995年 | 8篇 |
1994年 | 2篇 |
1993年 | 6篇 |
1992年 | 7篇 |
1991年 | 3篇 |
1990年 | 6篇 |
1989年 | 2篇 |
1988年 | 6篇 |
1987年 | 8篇 |
1986年 | 3篇 |
1985年 | 4篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1982年 | 5篇 |
1981年 | 1篇 |
1979年 | 3篇 |
1978年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1973年 | 3篇 |
1972年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有2504条查询结果,搜索用时 453 毫秒
121.
Fratelli M Demol H Puype M Casagrande S Villa P Eberini I Vandekerckhove J Gianazza E Ghezzi P 《Proteomics》2003,3(7):1154-1161
Protein glutathionylation is a post-translational modification consisting of the formation of a mixed disulfide between protein cysteines and glutathione (GSH). To identify proteins undergoing glutathionylation in primary rat hepatocytes and in human HepG2 hepatoma cells, we radiolabeled the intracellular GSH pool with L-[(35)S] cysteine. Cells were then exposed to oxidative stress. Proteins were separated by two-dimensional gel electrophoresis under nonreducing conditions, and glutathionylated proteins were located by autoradiography and identified by mass spectrometry after tryptic digestion. Several proteins previously not known to undergo glutathionylation were thus recognized. Among the identified proteins some are the same or belong to the same functional class as those we have already identified in a previous paper on T cell blasts (actin, nucleophosmin, phosphogluconolactonase, myosin, profilin, cyclophilin A, stress 70 protein, ubiquitin in HepG2 cells and actin, peroxiredoxin 5, cytochrome C oxidase, heat shock cognate 70 in hepatocytes) while others are newly recognized (Ran specific GTPase activating protein, histidine triad nucleotide binding protein 2 in HepG2 cells and enoyl CoA hydratase in hepatocytes). The technique described proved equally applicable to a variety of cell types. 相似文献
122.
Proteins from bovine tissues and biological fluids: defining a reference electrophoresis map for liver,kidney, muscle,plasma and red blood cells 总被引:1,自引:0,他引:1
Talamo F D'Ambrosio C Arena S Del Vecchio P Ledda L Zehender G Ferrara L Scaloni A 《Proteomics》2003,3(4):440-460
A number of high resolution two-dimensional electrophoresis (2-DE) reference maps for bovine tissues and biological fluids have been determined for animals in basal state. Among the 1863 distinct protein features detected in samples of liver, kidney, muscle, plasma and red blood cells, 509 species were identified and associated to 209 different genes. Difficulties in the identification were related to the poorly characterized Bos taurus genome and were solved by a combined matrix-assisted laser desorption/ionisation-mass spectrometry and liquid chromatography-electrospray ionization tandem mass spectrometry approach. The experimental output allowed us to establish a 2-DE database accessible through the World Wide Web network at the URL address (http://www.iabbam.na.cnr.it/Biochem). These reference maps may serve as a tool in future veterinary medical studies aimed at the evaluation of changes in protein repertoire for altered animal physiological conditions and infectious diseases, to the definition of molecular markers for novel diagnostic kits and vaccines, as well as the characterization of protein modifications in bovine materials following technological processes used in the food industry. 相似文献
123.
Melusin,a muscle-specific integrin beta1-interacting protein,is required to prevent cardiac failure in response to chronic pressure overload 总被引:13,自引:0,他引:13
Brancaccio M Fratta L Notte A Hirsch E Poulet R Guazzone S De Acetis M Vecchione C Marino G Altruda F Silengo L Tarone G Lembo G 《Nature medicine》2003,9(1):68-75
Cardiac hypertrophy is an adaptive response to a variety of mechanical and hormonal stimuli, and represents an early event in the clinical course leading to heart failure. By gene inactivation, we demonstrate here a crucial role of melusin, a muscle-specific protein that interacts with the integrin beta1 cytoplasmic domain, in the hypertrophic response to mechanical overload. Melusin-null mice showed normal cardiac structure and function in physiological conditions, but when subjected to pressure overload--a condition that induces a hypertrophic response in wild-type controls--they developed an abnormal cardiac remodeling that evolved into dilated cardiomyopathy and contractile dysfunction. In contrast, the hypertrophic response was identical in wild-type and melusin-null mice after chronic administration of angiotensin II or phenylephrine at doses that do not increase blood pressure--that is, in the absence of cardiac biomechanical stress. Analysis of intracellular signaling events induced by pressure overload indicated that phosphorylation of glycogen synthase kinase-3beta (GSK-3beta) was specifically blunted in melusin-null hearts. Thus, melusin prevents cardiac dilation during chronic pressure overload by specifically sensing mechanical stress. 相似文献
124.
To estimate changes in compliance, we evaluated the effects of sepsis on the end-diastolic pressure-volume relationship (EDPVR) in the left ventricle of rats that had undergone an open thorax procedure. Sepsis was induced in male Wistar Hannover rats (n = 7; 240 to 270 g) by intraperitoneal administration of a slurry of cecal contents; control rats (n = 7) were given 5% dextrose only. On the third day after induction of sepsis, left ventricular (LV) pressure and LV dimensions were recorded simultaneously in animals of both groups. Using a micromanometer and ultrasonic crystals, measurements were obtained at baseline and during the increase of afterload. Blood samples were taken for determination of complete blood count, white blood cell differential count, and lactate concentration, and for bacteriologic examination. Septic rats lost weight, and developed changes in body temperature, ascites, and abscesses in the abdominal and thoracic cavities, gram-negative bacteremia, and increase in heart rate. On the third day after induction of sepsis, LV EDPVR decreased, compared with that in the control rats (regression coefficients: control group, 8.41 to 23.95; sepsis group, 3.94 to 7.92). Myocardial compliance in the left ventricle increased on the third day of sepsis in the open-thorax rat model, as evidenced by the downward shift of LV EDPVR in rats with sepsis, compared with controls. 相似文献
125.
Antiendotoxin activity of protegrin analog IB-367 alone or in combination with piperacillin in different animal models of septic shock 总被引:1,自引:0,他引:1
Giacometti A Cirioni O Ghiselli R Mocchegiani F Viticchi C Orlando F D'Amato G Del Prete MS Kamysz W łLukasiak J Saba V Scalise G 《Peptides》2003,24(11):1747-1752
The therapeutic efficacy of protegrin peptide IB-367 was investigated in three rat models of septic shock: (i) rats injected intraperitoneally with 1mg Escherichia coli 0111:B4 lipopolysaccharide, (ii) rats given an intraperitoneal injection of 2 X 10(10) CFU of E. coli ATCC 25922, and (iii) rats in which intra-abdominal sepsis was induced via cecal ligation and puncture. All animals were randomized to receive parenterally isotonic sodium chloride solution, 1mg/kg of IB-367, 60mg/kg piperacillin and 1mg/kg of IB-367 plus 60mg/kg piperacillin. The peptide demonstrated lower level of antimicrobial activity than piperacillin, nevertheless it exhibited the dual properties of antimicrobial and antiendotoxin agent. Finally IB-367 and piperacillin association showed to be the most effective therapeutic approach. 相似文献
126.
Tatone C Delle Monache S Francione A Gioia L Barboni B Colonna R 《The International journal of developmental biology》2003,47(5):327-333
Protein kinase C (PKC), an enzyme playing a central role in signal transduction pathways, is activated in fertilized mouse eggs downstream of the fertilization Ca2+ signal, to regulate different aspects of egg activation. Given the presence of Ca2+-independent PKC isoforms within the egg, we investigated whether fertilization triggers PKC stimulation in mouse eggs by activating Ca2+-independent signalling pathways. An increase in PKC activity was detected as early as 10 min after the beginning of insemination, when about 90% of eggs had fused with sperm and the first Ca2+ rise was evident in most of the eggs. A similar level of activity was found 20 min later, when about 60% of eggs had resumed meiosis. When the Ca2+ increase was buffered by an intracellular Ca2+ chelating agent, PKC stimulation was not blocked but only slightly reduced. Confocal microscopy analysis revealed that the increase in PKC activity at fertilization coincided with the translocation of PKCdelta, a Ca2+-independent and diacylglycerol-dependent PKC isoform, to the meiotic spindle. When, in the absence of the Ca2+ signal, metaphase-anaphase transition was inhibited, PKCdelta moved to the meiotic spindle but still maintained a sustained cytoplasmic distribution. In summary, our results indicate that: 1) PKC activation is an early event of egg activation; 2) both Ca2+-dependent and Ca2+-independent pathways contribute to increased PKC activity at fertilization; 3) PKCdelta is one of the isoforms participating in this signalling process. 相似文献
127.
Giordano S 《Bioethics》2003,17(3):261-278
Imposing artificial feeding on people with anorexia nervosa may be unethical. This seems to be Heather Draper's suggestion in her article, 'Anorexia Nervosa and Respecting a Refusal of Life-Prolonging Therapy: A Limited Justification.' Although this is an important point, I shall show that the arguments supporting this point are flawed. Draper should have made a brave claim: she should have claimed that people with anorexia nervosa, who competently decide not to be artificially fed, should be respected because everybody is entitled to exercise their autonomy, not only 'in the middle' of their life, but also at the end of it, or when their own life is at stake, because autonomy also extends to the most difficult moments of our life, and, ultimately, 'stretches [.*T*.*T*.] far out into the distance' at the end of it. I explain why Draper should have made the brave claim, and why she has not made it. I conclude that a defence of people's entitlement to competently refuse artificial feeding cannot rest upon the arguments developed by Draper. Whether or not we should respect competent refusal of artificial feeding depends on the normative strength that we are ready to ascribe to the principle of autonomy, to the moral relevance that we ascribe to the circumstances in which a person's autonomy is exercised, and, perhaps, eventually, on our sense of compassion. 相似文献
128.
Prion diseases form a group of neurodegenerative disorders with the unique feature of being transmissible. These diseases involve a pathogenic protein, called PrP(Sc) for the scrapie isoform of the cellular prion protein (PrP(C)) which is an abnormally-folded counterpart of PrP(C). Many questions remain unresolved concerning the function of PrP(C) and the mechanisms underlying prion replication, transmission and neurodegeneration. PrP(C) is a glycosyl-phosphatidylinositol-anchored glycoprotein expressed at the cell surface of neurons and other cell types. PrP(C) may be present as distinct isoforms depending on proteolytic processing (full length and truncated), topology(GPI-anchored, transmembrane or soluble) and glycosylation (non- mono- and di-glycosylated). The present review focuses on the implications of PrP(C) glycosylation as to the function of the normal protein, the cellular pathways of conversion into PrP(Sc), the diversity of prion strains and the related selective neuronal targeting. 相似文献
129.
Trostchansky A Ferrer-Sueta G Batthyány C Botti H Batinić-Haberle I Radi R Rubbo H 《Free radical biology & medicine》2003,35(10):1293-1300
We have studied the role of three Mn(III)porphyrins differing in charge, alkyl substituent length and reactivity, on LDL exposed to low fluxes of peroxynitrite (PN) in the presence of uric acid. Mn(III)porphyrins (5 microM, MnTE-2-PyP(5+), MnTnOct-2-PyP(5+), and MnTCPP(3-)) plus uric acid (300 microM) inhibited cholesteryl ester hydroperoxide formation, changes in REM as well as spared alpha- and gamma-tocopherol. MnTnOct-2-PyP(5+), the more lipophilic compound, was the most effective in protecting LDL lipids, while MnTCPP(3-) exerted the lesser protection. Mn(III)porphyrins react fast with PN ( approximately 10(5)-10(7) M(-1) s(-1)) to yield a O=Mn(IV) complex. The stoichiometry of uric acid consumption was approximately 1.7 moles per mol of PN, in agreement with reactions with both the O=Mn(IV) complex and nitrogen dioxide. A shift from an anti- to a pro-oxidant action of the Mn(III)porphyrin was observed after uric acid was significantly consumed, supporting competition reactions between LDL targets and uric acid for the O=Mn(IV) complex. Overall, the data is consistent with the catalytic reduction of PN in a cycle that involves a one electron oxidation of Mn(III) to Mn(IV) by PN followed by the reduction back to Mn(III) by uric acid. These antioxidant effects should predominate under in vivo conditions having plasma uric acid concentration range between 150 and 500 microM. 相似文献
130.
Minutolo F Bertini S Betti L Danesi R Gervasi G Giannaccini G Papi C Placanica G Barontini S Rapposelli S Macchia M 《Bioorganic & medicinal chemistry letters》2003,13(24):4405-4408
Phosphonoacetamido(oxy) groups have proven to be good mimics of the diphosphate portion in geranylgeranyl protein transferase I (GGTase I) inhibitors. The introduction of small alkyl groups (Me, Et) into the diphosphate mimic moiety caused a further decrease in collateral farnesyl protein transferase (FTase) inhibitory activity, thereby improving GGTase I over FTase selectivity. 相似文献