全文获取类型
收费全文 | 8489篇 |
免费 | 259篇 |
国内免费 | 405篇 |
出版年
2023年 | 43篇 |
2022年 | 109篇 |
2021年 | 159篇 |
2020年 | 117篇 |
2019年 | 197篇 |
2018年 | 177篇 |
2017年 | 159篇 |
2016年 | 144篇 |
2015年 | 209篇 |
2014年 | 367篇 |
2013年 | 483篇 |
2012年 | 287篇 |
2011年 | 391篇 |
2010年 | 288篇 |
2009年 | 448篇 |
2008年 | 465篇 |
2007年 | 459篇 |
2006年 | 443篇 |
2005年 | 398篇 |
2004年 | 348篇 |
2003年 | 322篇 |
2002年 | 222篇 |
2001年 | 143篇 |
2000年 | 179篇 |
1999年 | 183篇 |
1998年 | 158篇 |
1997年 | 138篇 |
1996年 | 126篇 |
1995年 | 152篇 |
1994年 | 195篇 |
1993年 | 163篇 |
1992年 | 163篇 |
1991年 | 146篇 |
1990年 | 127篇 |
1989年 | 111篇 |
1988年 | 102篇 |
1987年 | 80篇 |
1986年 | 66篇 |
1985年 | 69篇 |
1984年 | 116篇 |
1983年 | 88篇 |
1982年 | 126篇 |
1981年 | 73篇 |
1980年 | 54篇 |
1979年 | 36篇 |
1978年 | 21篇 |
1977年 | 21篇 |
1976年 | 17篇 |
1975年 | 14篇 |
1971年 | 16篇 |
排序方式: 共有9153条查询结果,搜索用时 15 毫秒
71.
A B Van Kuilenburg A O Muijsers H Demol H L Dekker J J Van Beeumen 《FEBS letters》1988,240(1-2):127-132
Subunit VIII was purified from a preparation of the human heart cytochrome c oxidase and its complete amino acid sequence was determined. The sequence proved to be much more related to that of the bovine liver oxidase subunit VIII than to that found in bovine heart. Our finding of a ‘liver-type’ subunit VIII in the human heart enzyme suggests that either there are no isoforms of human subunit VIII or the human oxidase does not show the type of tissue specificity that has been reported for the oxidase in other mammals. 相似文献
72.
Phosphate-Activated Glutaminase in the Crude Mitochondrial Fraction (P2 Fraction) from Human Brain Cortex 总被引:1,自引:1,他引:0
Gerd Svenneby Bjørg Roberg Svein Hogstad Ingeborg Aa. Torgner Elling Kvamme 《Journal of neurochemistry》1986,47(5):1351-1355
The kinetics and other properties of phosphate-activated glutaminase have for the first time been studied in the crude mitochondrial fraction (P2 fraction) from human brain. The enzyme is for unexplained reasons inactivated postmortem. The enzyme activity decreases by storing the tissue or homogenate at 37 degrees C. The inactivation is not caused by formation of a dialysable inhibiting compound. No large proteolytic degradation has occurred, since the phosphate-activated glutaminase-like immunoreactive band did not disappear during the storage. The molecular weight of the subunit of the enzyme as determined by immunoblots of sodium dodecyl sulfate-treated homogenates from human brain is estimated to be approximately 64 K. The enzyme has been shown to have a pH optimum of 8.6; it is activated by phosphate, inhibited by glutamate, and partially inhibited by ammonia. Double-inverse plots of enzyme activity against phosphate are concave-upward, and more so in the presence of an inhibitor. The inhibition by glutamate appears to be noncompetitive with the substrate glutamine, and competitive with the activator phosphate. These kinetic properties are not significantly different from our earlier observations concerning phosphate-activated glutaminase from pig brain and pig kidney. 相似文献
73.
Siong-Chi Lin Kenneth C. Olson Haruo Okazaki† Elliott Richelson‡ 《Journal of neurochemistry》1986,46(1):274-279
Pirenzepine, a potent antimuscarinic agent with apparent selectivity for a subtype (M1) of muscarinic receptors, was used in tritiated form to characterize its binding to human brain tissue. Specific [3H]pirenzepine binding showed rapid association and dissociation. From kinetic and competitive binding experiments, its KD was 5.5 nM and 9 nM, respectively. Regional distribution of [3H]pirenzepine binding determined in parallel with [3H]quinuclidinyl benzilate binding, a nonselective muscarinic antagonist, indicated a significant correlation for the maximum number of binding sites for the two radioligands in 13 brain regions, with the highest amount of binding for each in the putamen and the least in the cerebellum. Binding for [3H]pirenzepine averaged 57% of that for [3H]quinuclidinyl benzilate, with a range of 20% (cerebellum) to 77% (frontal cortex). Most antidepressants and neuroleptics tested had affinities for [3H]pirenzepine binding sites that were not significantly different from their previously reported values obtained with the use of [3H]quinuclidinyl benzilate. 相似文献
74.
Quantitation of the Myelin-Associated Glycoprotein in Human Nervous Tissue from Controls and Multiple Sclerosis Patients 总被引:3,自引:2,他引:1
David Johnson Shuzo Sato Richard H. Quarles Takashi Inuzuka Roscoe O. Brady Wallace W. Tourtellotte 《Journal of neurochemistry》1986,46(4):1086-1093
Myelin-associated glycoprotein (MAG) was measured by radioimmunoassay in the human CNS and peripheral nervous system (PNS). The level of MAG, expressed as ng/microgram of total protein, was approximately 20-fold higher in whole homogenates of cerebral white matter (4.7 +/- 0.60) than of peripheral nerve (0.12-0.28). MAG concentrations were only slightly higher in the isolated myelin fractions from these tissues: CNS myelin, 5.6 ng/microgram; PNS myelin, 0.37 ng/microgram. The levels of MAG were measured in nine plaques, periplaque regions, and areas of macroscopically normal-appearing white matter (NAWM) from six separate multiple sclerosis brains and compared with the levels of other myelin proteins in the same samples. MAG and other myelin proteins were reduced to very low levels in plaques. The levels of MAG and basic protein (BP) and the activity of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) in periplaque areas were significantly lower than those in control white matter, and MAG and BP levels were also significantly reduced in NAWM. In a periplaque region and NAWM from the most rapidly progressing case of multiple sclerosis examined, the MAG content was between 30 and 35% of the control level, whereas BP and PLP levels and CNP activity were between 50 and 85% of control values. The reduction of MAG content in periplaque regions from all nine multiple sclerosis plaques examined was significantly greater than the reductions of BP level and CNP activity. In NAWM samples, the mean reduction of MAG content was also greater than the reductions of BP level and CNP activity, but the difference was only statistically significant in comparison to CNP.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
75.
Calcium-Activated Neutral Proteinase of Human Brain: Subunit Structure and Enzymatic Properties of Multiple Molecular Forms 总被引:6,自引:6,他引:0
Abstract Calcium-activated neutral proteinase (CANP) was purified 2,625-fold from postmortem human cerebral cortex by a procedure involving chromatography on diethylaminoethyl (DEAE)-cellulose, phenyl-Sepharose, Ultrogel AcA-44, and DEAE-Biogel A. The major active form of CANP exhibited a molecular weight of 94–100 kilodaltons (Kd) by gel filtration on Sephacryl 300 and consisted of 78-Kd and 27-Kd subunits. Two-dimensional gel electrophoresis resolved the small subunit into two molecular species with different isoelectric points. CANP degraded most human cytoskeletal proteins but was particularly active toward fodrin and the neurofilament protein subunits (145 Kd > 200 Kd > 70 Kd). The enzyme required 175 μMCa2+ for half-maximal activation and 2 mM Ca2+ for optimal activity toward [methl-14C]azocasein. Other divalent metal ions were poor activators of the enzyme, and some, including copper, lead, and zinc, strongly inhibited the enzyme. Aluminum, a neurotoxic ion that induces neurofilament accumulations in mammalian brain, inhibited the enzyme 47% at 1 mM and 100% at 5 mM A second CANP form lacking the 27-Kd subunit was partially resolved from the 100-Kd heterodimer during DEAE-Biogel A chromatography. The 78-Kd monomer exhibited the same specific activity, calcium ion requirement, pH optimum, and specificity for cytoskeletal proteins as the 100-Kd heterodimer, suggesting that the 27-Kd subunit is not essential for the major catalytic properties of the enzyme. The rapid autolysis of the 27-Kd subunit to a 18-Kd intermediate when CANP is exposed to calcium may explain differences between our results and previous reports, which describe brain mCANP in other species as a 76-80-Kd monomer or a heterodimer containing 76-80-Kd and 17-20-Kd subunits. The similarity of the 100-Kd human brain CANP to CANPs in nonneural tissues indicates that the heterodimeric form is relatively conserved among various tissues and species. 相似文献
76.
Biochemical Characterization of α-Adrenergic Receptors in Human Brain and Changes in Alzheimer-Type Dementia 总被引:2,自引:2,他引:0
Shun Shimohama Takashi Taniguchi Motohatsu Fujiwara Masakuni Kameyama 《Journal of neurochemistry》1986,47(4):1294-1301
Abstract Using ligand binding techniques, we studied α-adrenergic receptors in brains obtained at autopsy from seven histologically normal controls and seven patients with histopathologically verified Alzheimer-type dementia (ATD). Binding of the α-adrenergic antagonists [3H]prazosin and [3H]yohimbine to membranes of human brains exhibited characteristics compatible with α1- and α2-adrenergic receptors, respectively. Binding of both ligands was saturable and reversible, with dissociation constants of 0.15 nM for [3H]prazosin and 5.5 nM for [3H]yohimbine. [3H]Prazosin binding was highest in the hippocampus and frontal cortex and lowest in the caudate and putamen in the control brains. [3H]Yohimbine binding was highest in the nucleus basalis of Meynert (NbM) and frontal cortex and lowest in the caudate and cerebellar hemisphere in the control brains. Compared with values for the controls, [3H]prazosin binding sites were significantly reduced in number in the hippocampus and cerebellar hemisphere, and [3H]yohimbine binding sites were significantly reduced in number in the NbM in the ATD brains. These results suggest that α1 and α2-adrenergic receptors are present in the human brain and that there are significant changes in numbers of both receptors in selected regions in patients with ATD. 相似文献
77.
High-resolution proton magnetic resonance spectroscopy was used to analyze human cerebrospinal fluid obtained from patients with several neurological problems. The major metabolites measured included glucose, lactate, glutamine, citrate, inositol, acetate, creatine, creatinine, beta-hydroxybutyrate, alanine, and pyruvate. A drug vehicle, propylene glycol, was also measured. Alterations in the cerebrospinal fluid of these metabolites provided information concerning metabolism of the brain. Magnetic resonance spectroscopy offered a simple and rapid means of assessing these and other exogenous and endogenous compounds in diseases affecting the nervous system. 相似文献
78.
A. Filla G. De Michele V. Brescia Morra V. Palma A. Di Lauro G. Di Geronimo G. Campanella 《Journal of neurochemistry》1986,46(2):422-424
Glutamate dehydrogenase (GDH) activity was studied in 17 regions of six human brains. Duration and conditions of the postmortem period did not affect enzyme activity. Specific activity ranged between 103 and 377 nmoles/min/mg protein at 25 degrees C and it was 10-fold higher than that found in leukocytes. Apart from exclusively white matter regions (corpus callosum and centrum ovale), there was a moderate regional distribution (2.5-fold variation), with highest values in the inferior olive and hypothalamus, and lowest in the cerebellum and lenticular nucleus. With alpha-ketoglutarate (alpha-KG), NADH, or NH4+ as variable substrate, the apparent Km values in human brain were Km alpha-KG = 1.9 X 10(-3) M, KmNADH = 0.21 X 10(-3) M, and KmNH4+ = 28 X 10(-3) M, and in leukocytes they were Km alpha-KG = 1.7 X 10(-3) M, KmNADH = 0.24 X 10(-3) M, and KmNH4+ = 28 X 10(-3) M. The effects of cofactors, inhibitor, and pH were similar in brain and leukocyte GDH. 相似文献
79.
本文利用两株针对HAFP分子不同抗原决定簇的单克隆抗体,鉴定HAFP酶解片断的抗原抗体反应性质,并同完整HAFP分子进行比较。结果表明,酶解片断上失去了一株单克隆抗体所对应的分子部份,完整保留着另一株单克隆抗体所识别的抗原决定簇,从而证实HAFP分子某些抗原结构之间具有可分割性。 相似文献
80.
本文继先前工作后,进一步应用正常健康人外周血单个核细胞(PBMNC)经塑料培皿粘附技术把单核细胞分离出来,经培养进一步纯化,随后动态观察培养0,2,4,6和8天的单核-巨噬细胞的形态变化和对新鲜分离同种异基因个体PBMNC中NK活性的影响。实验表明,体外分化6天和8天的巨噬细胞质/核比例和胞浆内空泡显著增加,细胞直径约为0天时的2倍。这些细胞和PBMNC之比为0.5:1时,引起了NK细胞活性的50%以上抑制(4小时~(51)Cr标记K 562肿瘤的同位素释放试验)。这种抑制效应不为过氧化氢酶(Catalase 4000单位/毫升)和前列腺素合成酶的抑制剂(Indom 1×10~(-5)M)所阻断。实验证明,同种异基因个体的NK细胞不能识别巨噬细胞表面抗原,从而排除了巨噬细胞和K562肿瘤抗原竞争的可能性。实验还表明,巨噬细胞对NK活性的抑制是不受HLA约束的。应用高频超声振荡破碎巨噬细胞膜方法和免疫调变技术进一步提示,人体巨噬细胞对NK活性的抑制与巨噬细胞体积无关,而与体外分化所赋有的固有特性和它们分泌的免疫调节分子有关。 相似文献