全文获取类型
收费全文 | 3197篇 |
免费 | 349篇 |
国内免费 | 189篇 |
专业分类
耳鼻咽喉 | 16篇 |
儿科学 | 21篇 |
妇产科学 | 37篇 |
基础医学 | 817篇 |
口腔科学 | 37篇 |
临床医学 | 103篇 |
内科学 | 801篇 |
皮肤病学 | 29篇 |
神经病学 | 337篇 |
特种医学 | 34篇 |
外科学 | 167篇 |
综合类 | 390篇 |
预防医学 | 72篇 |
眼科学 | 51篇 |
药学 | 550篇 |
中国医学 | 127篇 |
肿瘤学 | 146篇 |
出版年
2024年 | 13篇 |
2023年 | 51篇 |
2022年 | 122篇 |
2021年 | 144篇 |
2020年 | 112篇 |
2019年 | 136篇 |
2018年 | 141篇 |
2017年 | 148篇 |
2016年 | 147篇 |
2015年 | 197篇 |
2014年 | 215篇 |
2013年 | 210篇 |
2012年 | 205篇 |
2011年 | 242篇 |
2010年 | 158篇 |
2009年 | 154篇 |
2008年 | 164篇 |
2007年 | 138篇 |
2006年 | 88篇 |
2005年 | 87篇 |
2004年 | 64篇 |
2003年 | 55篇 |
2002年 | 43篇 |
2001年 | 38篇 |
2000年 | 28篇 |
1999年 | 42篇 |
1998年 | 52篇 |
1997年 | 35篇 |
1996年 | 40篇 |
1995年 | 24篇 |
1994年 | 24篇 |
1993年 | 24篇 |
1992年 | 21篇 |
1991年 | 21篇 |
1990年 | 27篇 |
1989年 | 30篇 |
1988年 | 13篇 |
1987年 | 17篇 |
1985年 | 33篇 |
1984年 | 36篇 |
1983年 | 22篇 |
1982年 | 22篇 |
1981年 | 24篇 |
1980年 | 19篇 |
1979年 | 15篇 |
1978年 | 22篇 |
1977年 | 14篇 |
1976年 | 15篇 |
1975年 | 9篇 |
1973年 | 9篇 |
排序方式: 共有3735条查询结果,搜索用时 859 毫秒
11.
G. V. Chernysheva L. V. Stoida I. L. Kuz'mina 《Bulletin of experimental biology and medicine》1980,89(3):282-285
Keeping rabbits on a high-cholesterol diet (1 g/kg) for 3–7 months led to an increase in cholesterol concentration in the mitochondrial membranes and fragments of the sarcoplasmic reticulum (SPR) of the myocardium and skeletal muscles. Saturation of the membranes with cholesterol led to a decrease in efficiency of the Ca-pump of the SPR, as reflected in lowering of the Ca/ATP ratio and an increase in the outflow of Ca++ from the SPR. Under these conditions the rate of accumulation of Ca++ was higher in SPR than in the mitochondria. Activity of mitochondrial Mg++-activated 2,4-DNP-ATPase was reduced in hypercholesteremia.Laboratory of Molecular Pathology and Biochemistry, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 292–294, March, 1980. 相似文献
12.
Caffeine exerts a number of different effects on L-type calcium current in rat ventricular myocytes. These include: (1) a slowing of inactivation that is comparable to, but not additive to, that produced by prior treatment of the cells with ryanodine (a selective sarcoplasmic reticulum Ca2+ releaser) or high concentrations of intracellular 1,2-bis[2-aminophenoxy]ethane-N,N,N,N-tetraacetic acid (BAPTA) (a fast Ca2+ chelator), (2) a stimulation of peak I
Ca that is comparable to, but not additive to that produced by prior treatment with isobutylmethylxanthine (a selective phosphodiesterase inhibitor), and (3) a dose-dependent decrease of peak I
Ca that is not prevented by pretreatment with any of these agents. None of the caffeine actions could be mimicked or prevented by administration of 8-phenyltheophylline, a specific adenosine receptor antagonist. We conclude that only the slowing of I
Ca inactivation is due to caffeine's ability to deplete the sarcoplasmic reticulum of calcium. The stimulatory effect of caffeine on peak I
Ca is probably due to phosphodiesterase inhibition, while caffeine's inhibitory effect on I
Ca is independent of these processes and could be a direct effect on the channel. The multiplicity of caffeine actions independent of its effects on the sarcoplasmic reticulum lead to the conclusion that ryanodine, though slower acting and essentially irreversible, is a more selective agent than caffeine for probing sarcoplasmic reticulum function and its effects on other processes.The experimental part of this work was published during the postdoctoral stay of I. Zahradník in the Department of Physiology and Biophysics, The University of Texas Medical Branch, Galveston, TX 77555, USA 相似文献
13.
Class I molecules of the major histocompatibility complex bind peptides derived from cytosolic proteins and display them on the cell surface. This function alerts cytotoxic T cells to the presence of intracellular pathogens. Class I molecule assembly requires the association of the heavy chain with β2-microglobulin, accompanied by peptide loading via specific transporters. This study localizes where these assembly steps take place, using monoclonal antibodies recognizing class I molecules in different assembly states to analyze subcellular fractions of the early secretory pathway. The distribution of peptide-loaded class I molecules was more localized than the distribution of the total pool of class I molecules in the early secretory pathway. Loaded molecules colocalized with the peptide transporter, free heavy chains, and the chaperone calnexin in high density rough endoplasmic reticulum (RER) membranes. These data suggest that subunit assembly and peptide acquisition occur at the same intracellular site. Class I molecules also localized to less dense subfractions of the early secretory pathway, which contained comparatively less peptide-loaded molecules than the high density RER fractions, at steady state. Following a 15 °C temperature block, class I molecules accumulated in these less dense membrane fractions, indicating that these fractions represent the intermediate compartment where empty class I molecules are trapped in mutant cells. In the presence of cycloheximide, a pool of class I molecules recycling to the RER was detected, suggesting empty molecules recycle to acquire peptide. 相似文献
14.
培养细胞整装内质网三维结构的多态性 总被引:3,自引:0,他引:3
用高锰酸钾-锇酸固定法制备了5种培养细胞整装内质网标本,并在扫描电镜下对其三维结构进行了观察。观察结果表明内质网是由膜性小管构成的贯穿整个细胞质的管囊网络样膜性区室,并以多种形态深入到细胞伪足及突起中;细胞质中内质网则表现为簇状网络(见于GCM3T3细胞)、多态性多孔扁囊样网络、筛网状网络、条索状网络、大孔条索网状和细孔扁囊样分区网络、不规则管网状和多孔管囊分区网络(见于CV-1细胞)、细管网络(见于CCL187和CCL229细胞)、球囊网络(见于CCL187和A431细胞)和不规则管网状网络(见于A431细胞)等。内质网的这种多态性提示它是一种高度可变的结构,其可变性可能与细胞特性、分化程度、细胞功能状态及细胞骨架系统的分布变化等因素有关。 相似文献
15.
Masahiko Kuroda Hajime Horiuchi Teruaki Oka Tsuyoshi Ishida Akira Ono Masao Kawakita Rikuo Machinami 《Virchows Archiv : an international journal of pathology》1993,423(3):209-213
Ninety-one cases of human bone and soft tissue tumours were studied for calcium pump expression by strepto-avidin-biotin immunohistochemical staining with a monoclonal antibody against sarcoplasmic reticulum calcium-ATPase (mAb6F5). Two out of 5 cases of embryonal rhabdomyosarcoma, 1 out of 5 cases of biphasic synovial sarcoma, 4 of 4 cases of chordoma and all of 3 chondrosarcoma cases were positive for mAb6F5. Although this novel monoclonal antibody can be used as a marker of myogenic tumours, the present positive result for endoplasmic reticulum calcium-ATPase (calcium pump) in other tumours including chordoma, chondrosarcoma and synovial sarcoma indicates a wider immunoreactivity. The findings further suggest that intracellular calcium may play an important role in cell proliferation and/or differentiation. 相似文献
16.
The increased rate of Ca2+ uptake and ATPase activity in isolated cardiac sarcoplasmic reticulum (SR) by adenosine 3,5-monophosphate (cAMP) has been shown to be activated by a cAMP-dependent protein kinase (cAMP kinase). Functionally skinned myocardial fiber preparations were used to study the mechanisms of cAMP action on the SR at the same time that tension was monitored. cAMP effects were studied on Ca2+-activated tension of the contractile proteins, and on Ca2+ uptake and release from the SR using caffeine-induced tension transients. Neither cyclic AMP (0.1–5 M) nor the catalytic subunit of cAMP kinase (0.1–1 M) (PK-C) significantly changed either the maximal or the submaximal Ca2+-activated tension. The areas of the tension transients were unchanged when cAMP was present in the releasing solution (release phase), and were significantly increased up to a mean of about 80% when cAMP or PK-C was present in the Ca2+ loading solutions (uptake phase). The increased tension transient was blocked by the heat-stable inhibitor of cAMP kinase. We conclude that cAMP-induced increases in Ca2+ uptake by the SR could play an important role in the positive inotropic effect. cAMP kinase could thus play a crucial role in the regulation of myocardial contractility. 相似文献
17.
Mechanically skinned skeletal muscle fibres from rat and toad were exposed to the permeabilizing agents β-escin and saponin.
The effects of these agents on the sealed transverse tubular system (t-system) and sarcoplasmic reticulum (SR) were examined
by looking at changes in the magnitude of the force responses to t-system depolarization, the time course of the fluorescence
of fura-2 trapped in the sealed t-system, and changes in the magnitude of caffeine-induced contractures following SR loading
with Ca2+ under defined conditions. In the presence of 2 μg ml–1β-escin and saponin, the response to t-system depolarization was not completely abolished, decreasing to a plateau, and a
large proportion of fura-2 remained in the sealed t-system. At 10 μg ml–1, both agents abolished the ability of both rat and toad preparations to respond to t-system depolarization after 3 min of
exposure, but a significant amount of fura-2 remained in sealed t-tubules even after exposure to 100 μg ml–1β-escin and saponin for 10 min. β-Escin took longer than saponin to reduce the t-system depolarizations and fura-2 content
of the sealed t-system to a similar level. The ability of the SR to load Ca2+ was reduced to a lower level after treatment with β-escin than saponin. This direct effect on the SR occurred at much lower
concentrations for rat (2 μg ml–1β-escin and 10 μg ml–1 saponin) than toad (10 μg ml–1β-escin and 150 μg ml–1 saponin). The reverse order in sensitivities to β-escin and saponin of t-system and SR membranes indicates that the mechanisms
of action of β-escin and saponin are different in the two types of membrane. In conclusion, this study shows that: (1) β-escin
has a milder action on the surface membrane than saponin; (2) β-escin is a more potent modifier of SR function; (3) simple
permeabilization of membranes is not sufficient to explain the effects of β-escin and saponin on muscle membranes; and (4)
the t-system network within muscle fibres is not a homogeneous compartment.
Received: 18 November 1998 / Received after revision: 6 January 1999 / Accepted: 7 January 1999 相似文献
18.
19.
衰老是在细胞、组织和器官水平上发生的生理性内稳态的渐进性损害过程。就代谢角度而言,该过程主要表现为体成分、胰岛素抵抗、自噬功能障碍、线粒体和炎症反应的变化,其中涉及生长激素、胰岛素/胰岛素样生长因子1及各种能量感应系统如AMP活化蛋白激酶(AMP-activated protein kinase,AMPK). 相似文献
20.
C. H. Orchard G. L. Smith D. S. Steele 《Pflügers Archiv : European journal of physiology》1998,435(4):555-563
Rat ventricular trabeculae were mounted for isometric tension recording, and then permeabilized with saponin. The Ca2+ concentration ([Ca2+]) within the permeabilized preparation (cytosolic [Ca2+]) was monitored continuously using Indo-1 and the integrals of Ca2+ transients resulting from brief caffeine application used as an index of the sarcoplasmic reticulum (SR) Ca2+ content. The relationship between SR Ca2+ content and cytosolic [Ca2+] was studied within the reported physiological range (i.e. 50–250 nmol · l–1 Ca2+). Increasing cytosolic [Ca2+] from 50 nmol · l–1 to 250 nmol · l–1 increased the steady-state SR Ca2+ content about threefold. However, increasing [Ca2+] above 250 nmol · l–1 typically resulted in spontaneous SR Ca2+ release, with no further increase in SR Ca2+ content. The SR Ca2+ content increased only slowly when cytosolic [Ca2+] was increased; it was unchanged 20 s after a rapid increase in cytosolic [Ca2+], but increased progressively to a new steady-state level during the following 1–2 min. In a parallel series of experiments
using intact papillary muscles, increasing extracellular [Ca2+] (from 0.5 to 5 mmol · l–1) significantly increased twitch tension within 20 s of the solution change. These results support previous suggestions that
the SR Ca2+ content may increase when diastolic cytosolic [Ca2+] rises during inotropic interventions such as increased stimulus rate or extracellular [Ca2+]. However, the rate at which SR Ca2+ responds to changes in cytoplasmic [Ca2+] within the diastolic range does not appear rapid enough to explain the early potentiation of twitch tension in intact preparations
after an increase in extracellular [Ca2+].
Received: 26 August 1997 / Accepted: 28 October 1997 相似文献