全文获取类型
收费全文 | 438篇 |
免费 | 25篇 |
专业分类
463篇 |
出版年
2024年 | 1篇 |
2022年 | 4篇 |
2021年 | 9篇 |
2020年 | 2篇 |
2019年 | 6篇 |
2018年 | 12篇 |
2017年 | 9篇 |
2016年 | 7篇 |
2015年 | 13篇 |
2014年 | 11篇 |
2013年 | 24篇 |
2012年 | 26篇 |
2011年 | 28篇 |
2010年 | 13篇 |
2009年 | 11篇 |
2008年 | 18篇 |
2007年 | 23篇 |
2006年 | 38篇 |
2005年 | 32篇 |
2004年 | 27篇 |
2003年 | 17篇 |
2002年 | 14篇 |
2001年 | 12篇 |
2000年 | 4篇 |
1999年 | 10篇 |
1998年 | 5篇 |
1997年 | 4篇 |
1996年 | 6篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1992年 | 7篇 |
1991年 | 4篇 |
1990年 | 9篇 |
1989年 | 7篇 |
1988年 | 12篇 |
1987年 | 7篇 |
1986年 | 5篇 |
1985年 | 1篇 |
1984年 | 4篇 |
1983年 | 4篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1979年 | 4篇 |
1978年 | 1篇 |
排序方式: 共有463条查询结果,搜索用时 81 毫秒
1.
N. Yamada W. Murata Y. Yamaguchi K.-I. Fujita A. Ogita T. Tanaka 《Letters in applied microbiology》2021,72(4):390-398
Amphotericin B (AmB), a typical polyene macrolide antifungal agent, is widely used to treat systemic mycoses. In the present study, we show that the fungicidal activity of AmB was enhanced by benzyl isothiocyanate (BITC), a cruciferous plant-derived compound, in the budding yeast, Saccharomyces cerevisiae. In addition to forming a molecular complex with ergosterol present in fungal cell membranes to form K+-permeable ion channels, AmB has been recognized to mediate vacuolar membrane disruption resulting in lethal effects. BITC showed no effect on AmB-induced plasma membrane permeability; however, it amplified AmB-induced vacuolar membrane disruption in S. cerevisiae. Furthermore, the BITC-enhanced fungicidal effects of AmB significantly decreased cell viability due to the disruption of vacuoles in the pathogenic fungus Candida albicans. The application of the combinatorial antifungal effect of AmB and BITC may aid in dose reduction of AmB in clinical antifungal therapy and consequently decrease side effects in patients. These results also have significant implications for the development of vacuole-targeting chemotherapy against fungal infections. 相似文献
2.
S Ogita M Imanaka T Takebayashi Y Nakai H Fukumasu S Matsuo M Matsumoto B Tanaka K Iwanaga 《The Annals of physiological anthropology》1990,9(2):93-98
For the purpose of determining the most reasonable lying posture for pregnant women, we investigated the lying positions of both 247 non-pregnant women and 302 pregnant women during sleep. As for the rate of each position during the entire period of observation, 33.2% of the non-pregnant women were in the supine position, 41.2% in the lateral position, 18.4% in Sims' position and 7.1% in the prone position. In the pregnant group, the rate of supine position, simple lateral position and Sims' position was 34.2%, 52.2% and 12.7%, respectively, but the rate of the prone position was limited to 0.8%. All of the gravidas assuming the prone position were at less than 16 weeks of gestation. Non-pregnant women could sleep in a variety of positions, but pregnant women could assume the prone position during sleep only in the stage when the abdomen is not yet prominent or distended. Pregnant women were restricted significantly, either consciously or unconsciously, with progress in gestation. 相似文献
3.
The heterogeneity and differential expression of protein kinase C in nervous tissues 总被引:1,自引:0,他引:1
4.
Zymogen-activating factors in the mouse were investigated by two-dimensional electrophoresis. Mouse pancreatic zymogens--trypsinogen-I group (Try G-I group), trypsinogen-II (Try G-II), and chymotrypsinogen (Chy G)--were purified using DEAE-cellulose column chromatography. Analysis by two-dimensional electrophoresis, using the purified zymogens as substrates, revealed enterokinase isozymes and chymotrypsinogen-activating factors in both the intestinal extract and luminal fluid. Mouse enterokinase was separated into at least two bands in the first-dimensional gel, each able to activate both trypsinogens Try G-I group and Try G-II. Chymotrypsinogen-activating factors were separated into several bands in the first-dimensional gel. Some activating factors showed mobilities similar to those of mouse enterokinase isozymes. Moreover, other activating factors that can activate chymotrypsinogen were present only in the more anodal area of the first-dimensional gel. These findings indicate that at least two enterokinases and several chymotrypsinogen-activating factors play an important role in the process of activating digestive enzymes. 相似文献
5.
Masahiro Okazaki Nobuyuki Yanagihara Futoshi Izumi Yasuhide Nakashima Akio Kuroiwa 《Journal of neurochemistry》1989,52(1):222-228
The distribution and secretion of atrial natriuretic peptides (ANPs) were investigated in bovine adrenal medulla. (1) Cultured bovine adrenal medullary cells (2 x 10(6)/dish) contained 100.4 +/- 6.0 fmol of immunoreactive ANP (IR-ANP) and 207.3 +/- 6.6 nmol of catecholamines as epinephrine plus norepinephrine. (2) Stimulation of nicotinic but not muscarinic acetylcholine receptors caused a cosecretion of IR-ANP and catecholamines corresponding to the ratio of IR-ANP to catecholamines in cultured bovine adrenal medullary cells. (3) Carbachol-stimulated secretion of IR-ANP was dependent on the presence of extracellular Ca2+. (4) Chromaffin granules isolated from bovine adrenal medulla contained large amounts of IR-ANP and catecholamines, in the same ratio as did cultured adrenal medullary cells. (5) Reverse-phase HPLC analysis showed that both stored and secreted IR-ANP consisted of two components, which eluted at the position of ANP(99-126) or ANP(1-126). These results indicate that ANPs are stored as ANP(99-126) and ANP(1-126) in chromaffin granules, and are cosecreted in parallel with catecholamines in a Ca2+-dependent manner by the stimulation of nicotinic acetylcholine receptors. 相似文献
6.
7.
Further Evidence for Multiple Forms of an N-Methyl-d-Aspartate Recognition Domain in Rat Brain Using Membrane Binding Techniques 总被引:1,自引:1,他引:0
Pingping Zuo Kiyokazu Ogita Takeo Suzuki Daiken Han Yukio Yoneda 《Journal of neurochemistry》1993,61(5):1865-1873
Abstract— Pretreatment with sulfhydryl-reactive agents, such as N-ethylmaleimide and p-chloromercuriphenylsul-fonic acid, invariably resulted in marked inhibition of the binding of dl -(E)-2-amino-4-[3H]propyl-5-phosphono-3-pentenoic acid ([3H]CGP 39653), a competitive antagonist at an N-methyl-d -aspartate (NMDA)-sensitive subclass of central excitatory amino acid receptors, in brain synaptic membranes extensively washed and treated with Triton X-100, but did not significantly affect the binding of L-[3H]-glutamic acid ([3H]Glu), an endogenous agonist. The pre-treatment was effective in reducing the binding of [3H]-CGP 39653 at equilibrium, without altering the initial association rate, and decreased the affinity for the ligand. Pretreatment with sulfhydryl-reactive agents also enhanced the potencies of NMDA agonists to displace [3H]-CGP 39653 binding and attenuated those of NMDA antagonists, but had little effect on the potencies of the agonists and antagonists to displace [3H]Glu binding. The binding of both [3H]CGP 39653 and [3H]Glu was similarly sensitive to pretreatment with four different proteases in Tritontreated membranes, whereas pretreatment with phospho-lipase A2 or C markedly inhibited [3H]CGP 39653 binding without altering [3H]Glu binding. Moreover, both phospho-lipases not only induced enhancement of the abilities of NMDA agonists to displace the binding of [3H]CGP 39653 and [3H]Glu, but also caused diminution of those of NMDA antagonists. These results suggest that both sulfhydryl-reactive agents and phospholipases may predominantly interfere with radiolabeling of the NMDA recognition domain in a state favorable to an antagonist by [3H]CGP 39653, with concomitant facilitation of that in an agonist-preferring form by [3H]Glu. The possible presence of multiple forms of the NMDA recognition domain is further supported by these data. 相似文献
8.
Abstract: Pretreatment with Triton X-100 more than doubled the binding of radiolabeled 5,7-dichlorokynurenic acid (DCKA), a proposed antagonist at a glycine (Gly) recognition domain on the N-methyl-d -aspartate (NMDA) receptor ionophore complex, in rat brain synaptic membranes. The binding exhibited an inverse temperature dependency, reversibility, and saturability, the binding sites consisting of a single component with a high affinity (27.5 nM) and a relatively low density (2.87 pmol/mg of protein). The binding of both [3H]DCKA and [3H]Gly was similarly displaced by numerous putative agonists and antagonists at the Gly domain in a concentration-dependent manner at a concentration range of 100 nM to 0.1 mM. Among the 24 putative ligands tested, DCKA was the second most potent displacer of the binding of both radioligands with no intrinsic affinity for the binding of [3H]kainic acid and α-amino-3-hydroxy-5-[3H]methylisoxazole-4-propionic acid (AMPA) to the non-NMDA receptors. In contrast, the other proposed potent Gly antagonist, 5,7-dinitroquinoxaline-2,3-dione, was active in displacing the binding of [3H]glutamic ([3H]Glu) and D,L-(E)-2-amino-4-[3H]propyl-5-phosphono-3-pentenoic acids to the NMDA recognition domain with a relatively high affinity for the non-NMDA receptors. In addition, the proposed antagonist at the AMPA-sensitive receptor, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline, not only displaced weakly the binding of both [3H]- Gly and [3H]DCKA, but also inhibited the binding of (+)-5-[3H]methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine ([3H]MK-801) to an ion channel associated with the NMDA-sensitive receptor in the presence of added Glu alone in a manner sensitive to antagonism by further added Gly. Clear correlations were seen between potencies of the displacers to displace [3H]DCKA binding and [3H]Gly binding, in addition to between the potencies to displace [3H]-DCKA or [3H]Gly binding and to potentiate or inhibit [3H]MK-801 binding. All quinoxalines tested were invariably more potent displacers of [3H]DCKA binding than [3H]Gly binding, whereas kynurenines were similarly effective in displacing the binding of both [3H]Gly and [3H]-DCKA. These results undoubtedly give support to the proposal that [3H]DCKA is one useful radioligand available in terms of its high selectivity and affinity for the Gly domain in the brain. Possible multiplicity of the Gly domain is suggested by the differential pharmacological profiles between the binding of [3H]Gly and [3H]DCKA. 相似文献
9.
Futoshi Aranishi Kenji Hara Kiyoshi Osatomi Tadashi Ishihara 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》1996,114(4):371-376
Cathepsin B was purified from the crude extract of carp (Cyprinus carpio) hepato-pancreas by the method involving ammonium sulfate fractionation and five sequential chromatographies monitored the activity with Z-Arg-Arg-MCA as a substrate, and the specific activity increased about 11,400 fold with a 2% recovery. Although the homogeneity of the purified cathepsin B was established on Native-PAGE, it migrated as two bands of 29,000 and 25,000 molecular weights by the single and heavy chains on SDS-PAGE, respectively. The monospecific antibody against the homogeneous cathepsin B was purified by the affinity chromatography on cathepsin B-Sepharose 4B, and did not immunologically react with rat cathepsin B, carp cathepsins H and L but only with carp cathepsin B by immunoelectrophoretic blot analysis. As the result of the tissue and liver distributions of cathepsin B, the remarkable immunological reactivities in the extracts of spleen, kidney and hepato-pancreas in carp and those of pacific cod, yellow fin tuna, skip jack tuna and common mackerel in pisces were detected with the anti-carp hepato-pancreas cathepsin B at molecular weight of nearby 29,000 or 25,000. 相似文献
10.
Summary Processes in the development of intestinal metaplasia of the stomach were investigated from the morphological and histochemical approaches using light and electron microscopic techniques. The specimens taken from 38 gastric carcinomas and 15 gastric and/or duodenal ulcers were subjected to this study. Morphological appearances of the intestinal metaplasia observed in routine examination with hematoxylin and eosin staining was able to be divided into complete and incomplete metaplasia by the light and electron microscopic histochemical stainings of the mucosubstances. The columnar cells at the area of the incomplete metaplasia had both the properties of the intestinal epithelia and the gastric foveolar epithelia. The incomplete as well as the complete metaplasia arose from the generative cells at the isthmus of the gland. The generative cells, however, sometimes gradually transformed to produce the complete metaplastic cells. The two processes of the development of the intestinal metaplasia were proposed and discussed. 相似文献