全文获取类型
收费全文 | 4040篇 |
免费 | 192篇 |
国内免费 | 165篇 |
专业分类
耳鼻咽喉 | 31篇 |
儿科学 | 24篇 |
妇产科学 | 16篇 |
基础医学 | 709篇 |
口腔科学 | 169篇 |
临床医学 | 150篇 |
内科学 | 648篇 |
皮肤病学 | 12篇 |
神经病学 | 653篇 |
特种医学 | 84篇 |
外科学 | 252篇 |
综合类 | 540篇 |
预防医学 | 239篇 |
眼科学 | 26篇 |
药学 | 720篇 |
中国医学 | 85篇 |
肿瘤学 | 39篇 |
出版年
2024年 | 6篇 |
2023年 | 20篇 |
2022年 | 53篇 |
2021年 | 78篇 |
2020年 | 90篇 |
2019年 | 59篇 |
2018年 | 83篇 |
2017年 | 59篇 |
2016年 | 68篇 |
2015年 | 69篇 |
2014年 | 161篇 |
2013年 | 191篇 |
2012年 | 165篇 |
2011年 | 215篇 |
2010年 | 201篇 |
2009年 | 206篇 |
2008年 | 216篇 |
2007年 | 236篇 |
2006年 | 188篇 |
2005年 | 178篇 |
2004年 | 182篇 |
2003年 | 167篇 |
2002年 | 110篇 |
2001年 | 115篇 |
2000年 | 94篇 |
1999年 | 101篇 |
1998年 | 130篇 |
1997年 | 102篇 |
1996年 | 71篇 |
1995年 | 74篇 |
1994年 | 87篇 |
1993年 | 71篇 |
1992年 | 61篇 |
1991年 | 67篇 |
1990年 | 61篇 |
1989年 | 55篇 |
1988年 | 51篇 |
1987年 | 55篇 |
1986年 | 35篇 |
1985年 | 28篇 |
1984年 | 31篇 |
1983年 | 15篇 |
1982年 | 22篇 |
1981年 | 18篇 |
1980年 | 14篇 |
1979年 | 9篇 |
1978年 | 5篇 |
1977年 | 11篇 |
1976年 | 7篇 |
1973年 | 2篇 |
排序方式: 共有4397条查询结果,搜索用时 0 毫秒
21.
Michael A. Rogawski 《Naunyn-Schmiedeberg's archives of pharmacology》1988,338(2):125-132
Summary Whole cell voltage-clamp recordings from GH3 cells, a clonal cell line derived from a rat anterior pituitary tumor, demonstrated a rapidly activating and inactivating (transient) voltage-dependent outward current. This current, referred to as I
A, was elicited by step depolarization from holding potentials negative to –50 mV, showed strong outward rectification at potentials positive to –30 mV, and exhibited steady state inactivation with V
1/2 near –64 mV. The current rose to a peak within < 10–20 ms following depolarization and decayed in two exponential phases, I
Af and IA
AS with time constants of 30–50 and 500–700 ms, respectively. Both I
A components exhibited similar voltage dependencies for activation and inactivation. Aminopyridines (2 mol/l – –5 mmol/l) produced a dose dependent, reversible blockade of I
A (70% inhibition at 0.5 to 2 mmol/l) with the following rank order of potencies: 4-aminopyridine > 3,4-diaminopyridine = 3-aminopyridine > 2-aminopyridine. These drugs reduced the peak conductance of I
A, and produced complex effects on its time-dependent decay. With submaximal degrees of block, there was an increase in the inactivation rate, suggesting that open channels are preferentially blocked by the drugs. It is concluded that GH3 pituitary cells possess an aminopyridine-sensitive transient outward current comparable to the A-current in neural cells. However, this cell line is unusual in that it expresses both rapidly and slowly decaying A-current components.Abbreviations
n-AP
n-aminopyridine
- 3,4-DAP
3,4-diaminopyridine
- TEA
tetraethylammonium
- EGTA
ethylene glycol bis(-aminoethyl ether)N,N-tetraacetic acid
- HEPES
4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid
Send offprint requests to M. A. Rogawski at the above address 相似文献
22.
G. I. Sandle G. Fraser S. Long G. Warhurst 《Pflügers Archiv : European journal of physiology》1990,417(3):259-263
Hydrochloric acid (HCl) secretion by gastric parietal cells involves an apical Cl– conductance, the properties of which have not been defined. In the present study, forskolin and histamine [agonists that increase intracellular cyclic adenosine monophosphate (cAMP)], and dibutyryl cAMP, activated channels in previously quiescent cell-attached membrane patches on cultured human gastric cells (HGT-1). In the cell-attached configuration (Cl–149 mmol/ 1 in bath and pipette), channels exhibited outward rectification, voltage dependence, inward current (–0.7 pA) at zero holding potential and a reversal potential of +24 mV, consistent with the presence of a Cl– conductive pathway. In excised inside-out patches, channels (i) exhibited degrees of outward rectification and voltage dependence that were comparable to those seen in cell-attached patches, (ii) demonstrated a –21 mV shift of their reversal potential when bath Cl– was decreased from 149 mmol/l to 53 mmol/l (calculated Cl–:cation permeability ratio 171), and (iii) were highly sensitive to the Cl– channel blocker diphenylamine-2-carboxylic acid (DPC, 10–3 mol/l). This cAMP-activated Cl– channel bears many similarities to other Cl– channels within intestinal epithalia, and may represent the apical Cl– channel operating in HCl-secreting gastric parietal cells. 相似文献
23.
Ove Christensen Marek Simon Torben Randlev 《Pflügers Archiv : European journal of physiology》1990,415(1):37-46
We have used the patch-clamp technique to characterize three anion channels in the ventricular membrane of the choroid plexus epithelium from Necturus. The most frequently occurring channel had a nonlinear IV-curve. The conductance in excised patches with 112 mM chloride at both sides was 28 pS at 0 mV, increasing towards positive membrane potentials. The selectivity ratios were P
NaP
Cl 0.1 and
. SITS and furosemide (1 mM) on the inside reduces chloride flux to 0.15 and 0.37 times the control value. In attached patches, the most commonly observed channel had a conductance of 7.5 pS. The single-channel current for this channel reversed direction at 15 mV hyperpolarization, indicating accumulation of chloride to a factor of 1.8 above equilibrium. External stimulation of the tissue by theophylline, IBMX and dbcAMP, or by hypotonic shock did not increase the activity of this channel. In very few excised patches, we have observed a chloride channel with a conductance of 7 pS with 112 mM chloride at both sides. The 7 pS channel appears to be identical to a 2 pS channel found in attached patches. The 2 pS channel was not normally active in attached patches but was activated in 28% of the patches by external stimulation. Finally, in few excised patches we have found a 375 pS channel which inactivates within seconds when membrane potential is stepped from 0 mV to a value that differs more than 10–20 mV from zero. The channel did not conduct gluconate but
and P
NaP
Cl 0.1. Internal SITS and furosemide (1 mM) reduced chloride flux to 0.3 and 0.5 times the control value. The channel was never seen in attached patches. The current carried through these channels can not account for the transepithelial steady state Cl–-flux measured by microelectrodes. KCl exit from the cell is suggested to be carried by KCl-cotransport or by channels that are too small to be seen in patch-clamp experiments. 相似文献
24.
Mohammad Nasri-Sebdani Flavien Traoré Christian Cognard Daniel Potreau Jean -Pierre Poindessault Guy Raymond 《Pflügers Archiv : European journal of physiology》1990,416(1-2):106-112
The effects of tetracaine (10–50 M) and ryanodine (0.1–10 M) were tested on the slow outward K+ current (I
so) and the mechanical tension of isolated frog muscle fibres in a voltage-clamp device (double mannitol-gap) connected to a mechanoelectric transducer. In the concentration range tested, both drugs induced a simultaneous inhibition of tension and current. In all cases the effect on tension was twice that on current. The tetracaine-induced current and tension blocks were fully reversible and dose-dependent. In contrast the ryanodine effects on current and tension were not reversible and did not exhibit a dose dependence except for the delay before the onset of the response, which was shortened when the concentration was raised. Linear regression analysis of the time-dependent and dose-dependent effects of both drugs indicated a strong correlation between the decreases in tension and current. It is concluded that the slow outward current is partly under the control of the Ca2+ release from sarcoplasmic reticulum during contraction. 相似文献
25.
Conductance properties and voltage dependence of an anion channel in amphibian skeletal muscle 总被引:3,自引:0,他引:3
Single anion-selective channels were studied in excised membrane patches of adult frog toe muscle. The conductance and the probabilityp
o of the main open state were determined for various ionic compositions of the extra-and intracellular solutions. =280 pS in symmetrical 110 mM NaCl, pH 7.4 solutions at 15°C. Higher values were found at elevated internal or external NaCl concentrations, in 70 mM external CaCl2 and at lower extracellular pH. Thep
o(E) curve declined steeply with hyperpolarization and was shifted towards more negative potentials at increased internal ionic strength and at higher external pH. Positive shifts were induced by extracellular Ca. The results show that the anion channel saturates at Cl concentrations >110 mM, that the potential profile of an open channel is almost symmetrical and that channel gating is affected by neighboring channels. It is suggested that the anion channel has a voltage sensor (effective gating charge 4.3) and a similar collection of local fixed charges on the extra- and intracellular sides as voltage-gated cation channels. 相似文献
26.
The volume-activated chloride current in endothelial cells from bovine pulmonary artery is not modulated by phosphorylation 总被引:8,自引:0,他引:8
Géza Szücs Stephan Heinke Christine De Greef Luc Raeymaekers Jan Eggermont Guy Droogmans Bernd Nilius 《Pflügers Archiv : European journal of physiology》1996,431(4):540-548
We employed the patch-clamp technique to investigate the effects of various phosphorylation pathways on activation and modulation of volume-activated Cl- currents (I
Cl,vol) in cultured endothelial cells from bovine pulmonary arteries (CPAE cells). Half-maximal activation ofI
Cl,vol occurred at a hypotonicity of 27.5 ± 1.2%. Run-down of the current upon repetitive activation was less than 15% within 60 min. Stimulation of protein kinase C (PKC) by phorbol-12-myristate-13-acetate (PMA) or by (–)-indolactam did not affectI
Cl,vol. Down regulation of PKC activity by a 24-h preincubation of the cells with 0.2 mol/l PMA, or its inhibition by loading the cells with the specific inhibitory 19–31 pseudosubstrate peptide, did not influenceI
Cl,vol. Trifluoperazine and tamoxifen fully blockedI
cCl,vol with concentrations required for half-maximal inhibition of 3.0 and 2.4 mol/1 respectively. This inhibitory effect is probably not mediated by the calmodulin-antagonistic action of these compounds, because it occurs at free intracellular [Ca2+] of 50 nmol/l, which are below the threshold for calmodulin activation. The tyrosine kinase inhibitor herbimycin A (1 ol/1) and genistein (100 ol/1) did not affectI
Cl,vol Exposing CPAE cells to lysophosphatidic acid (1mol/1), an activator of p42 MAPkinase and the focal adhesion kinase p125FAK in endothelial cells, neither evoked a Cl– current nor affectedI
Cl,vol Neither wortmannin (10 mol/1), an inhibitor of MAP kinases and of PI-3 kinase, nor rapamycin (0.1 mmol/1), which interferes with the p70S6 kinase pathway, affectedI
Cl,vol Exposure of CPAE cells to heat or Na-arsenite, both activators of a recently discovered stress-activated tyrosine phosphorylation pathway, neither activated a current nor affected the hypotonic solution-induced Cl– current. We conclude that none of the studied phosphorylation pathways is essential for the activation of the Cl– current induced by hypotonicity. 相似文献
27.
Heinz Gögelein Eberhard Schlatter Rainer Greger 《Pflügers Archiv : European journal of physiology》1987,409(1-2):122-125
Besides the larger Cl– channel with a single channel conductance of about 45 pS, a small channel was observed in the luminal membrane of the dogfish rectal gland [9]. In cell excised (inside out) patches with NaCl solution on both sides, the latter channel had a single channel conductance of 11±1 pS (n=21), and its current-voltage relationship was linear in the voltage range+90 to –90 mV. The open state probability increased moderately with negative clamp potentials. Ionic replacement studies revealed a high selectivity of Cl– over gluconate, sulfate, and iodide, whereas bromide was permeable to some extent. Also the channel is impermeable for Na+. The Cl– channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoate did not affect this small conductance Cl– channel. It can be concluded that the luminal membrane of stimulated rectal gland cells possesses two types of Cl– channels, which differ markedly in their characteristics.Supported by Deutsche Forschungsgemeinschaft Gr 480/8 and by NSF and NIH grants to the MDIBL 相似文献
28.
Stanley G. Rane George G. Holz IV Kathleen Dunlap 《Pflügers Archiv : European journal of physiology》1987,409(4-5):361-366
Dihydropyridine (DHP) calcium channel antagonists, which inhibit the slowly inactivating or L-type cardiac calcium (Ca) current, have been shown to be ineffective in blocking45Ca influx and Ca-dependent secretion in a number of neuronal preparations. In the studies reported here, however, the antagonist DHP nifedipine inhibited both the L-type Ca current and potassium-evoked substance P (SP) release from embryonic chick dorsal root ganglion (DRG) neurons. These results suggest that, in DRG neurons. Ca entry through L-type channels is critical to the control of secretion. The inhibition of Ca current by nifedipine was both voltage and time-dependent, significant effects being observed only on currents evoked from relatively positive holding potentials maintained for several seconds. As expected from these results, nifedipine failed to inhibit L-type Ca current underlying the brief plateau phase of the action potential generated from the cell's normal resting potential; likewise, no significant effect of the drug was observed on action potential-stimulated SP release evoked by electrical field stimulation. The results of this work are discussed in terms of an assessment of the role of L-type Ca channels in neurosecretion.This work was supported by United States Public Health Service Grant NS16483 (KD) and by a USPHS Postdoctoral Fellowship (SGR) 相似文献
29.
W. -M. Weber K. M. Liebold F. W. Reifarth U. Uhr W. Clauss 《Pflügers Archiv : European journal of physiology》1995,429(6):820-824
Removal of Ca2+ from the external bath solution evoked marked depolarization and large currents (up to several microamperes) in voltage-clamped defolliculated oocytes of Xenopus laevis. The resulting current was not carried by a cation influx but was due to a huge Cl– efflux, which could be strongly inhibited by the Cl– channel blockers flufenamic acid and niflumic acid. Removal of Mg2+ or Ba2+ from the solutions had the same effects as removing Ca2+. The reversal potential of –12 mV also indicated that Cl– channels were responsible for the large currents. Patch-clamp studies revealed a single-channel slope conductance of 90 pS. During oocyte maturation these channels remained active. The half-maximal Ca2+ concentration of about 20 M showed that quite low doses of extracellular Ca2+ profoundly influence the electrical properties of the oocyte membrane. 相似文献
30.
Abstract Aim: The gas molecule nitric oxide (NO) has been shown to modulate autonomic function by acting both peripherally and centrally. Accumulating evidence indicates that the paraventricular nucleus (PVN) of the hypothalamus is an important locus mediating central NO actions on autonomic function, under both physiological and pathological conditions. However, the cellular targets and mechanisms mediating NO actions within the PVN are still poorly understood. Results: By combining in vitro patch‐clamp recordings with neuronal tract tracing techniques, we show that neuronal excitability of autonomic‐related neurones in the PVN is tonically inhibited by an endogenous NO input. Furthermore, immunohistochemical studies show that ~25% of autonomic‐related PVN neurones express neuronal nitric oxide synthase, suggesting that at least a proportion of them contribute to the cellular sources of NO within the PVN. Conclusion: In summary, this work suggests that NO modulation of the firing activity of autonomic‐related PVN neurones constitutes an efficient mechanism mediated central NO regulation of autonomic function. 相似文献