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排序方式: 共有458条查询结果,搜索用时 15 毫秒
1.
2.
M. Bergström G. Westerberg G. Németh M. Traut G. Gross G. Greger H. Müller-Peltzer A. Safer S.-Å. Eckernäs A. Grahnér B. Långström 《European journal of clinical pharmacology》1997,52(2):121-128
Objective: The aim of the study was to investigate whether or not esuprone binds substantially to MAO-A in the human brain. Methods: In a randomised double-blind placebo-controlled study 16 male healthy volunteers were examined␣with positron emission tomography
(PET) with [11C]harmine. Eight of the volunteers were given daily doses of 800 mg esuprone, four were given bi-daily doses of 300 mg moclobemide,
and four volunteers were given placebo tablets. PET was performed before initiation of a 7-day treatment period. On day 7,
one investigation was made immediately before administration of the drug, representing 23 h after the previous day's treatment
for esuprone and 11 h after the last tablets of moclobemide. Further investigations were made 4 h and 8 h after the morning
dose on day 7. Results: PET showed a high degree of binding of [11C]harmine, a high-affinity ligand for MAO-A, before the start of treatment, and a marked and similar reduction after treatment
with esuprone and moclobemide. A slight tendency for normalisation of enzyme binding was observed at the last time point.
In the placebo group no change was observed. Plasma kinetics of esuprone showed a rapid elimination with a half-life of about
4 h. Conclusion: The study demonstrates that esuprone was comparable to moclobemide in its effect on MAO-A inhibition in the brain at the
doses given. This is an illustration of the potential of PET to monitor drug effects directly on target biochemical systems
in the brain in human volunteers, and the possibility of using these data, rather than pharmacokinetic data, for the determination
of dosing intervals.
Received: 21 August 1996 / Accepted in revised form: 22 November 1996 相似文献
3.
E. Schlatter U. Fröbe R. Greger 《Pflügers Archiv : European journal of physiology》1992,421(4):381-387
The study of ion conductances in the intact cortical collecting duct (CCD) with the patch-clamp method is rather difficult. An optimized method to isolate CCD cells from rat kidneys using an in vivo followed by an in vitro enzyme digestion is described. Individual CCD segments were collected after this digestion and incubated in EGTA-buffered medium. This procedure resulted in single cells or cell clusters. These freshly isolated CCD cells were studied with different modifications of the patch-clamp method. Membrane voltages measured in the cell-attached-nystatin configuration were –74 ±1mV (n=13) and –68±3 mV (n=22) in cells isolated from normal and mineralocorticoid-treated rats respectively. These values and those measured with the nystatin-perforated slow-whole-cell configuration (–79 ±1mV, n=23) are comparable to those measured in principal cells of isolated CCD segments. The cells hyperpolarized after the addition of amiloride and depolarized with the addition of adiuretin to the bath. The amiloride effect was enhanced when cells were isolated from deoxycorticosterone-acetate-treated rats. The cells were strongly depolarized upon elevation of the extracellular K+-concentration and did not demonstrate a measurable Cl– conductance. A large-conductance K+ channel (174 pS, n=5, cell-attached, 145 mmol/l K+ in the pipette; 140 pS, n=12, cell-free, 3.6 mmol/l K+ in the bath) was seen. It had a very low activity on the cell, but a high open probability when excised into a solution with 1 mmol/l Ca2+ on the cytosolic side. More often a small-conductance K+ channel (36–52 pS, n=19, cell-attached; 30 pS, n=5, cell-free) with a high open probability was found on the cell. These freshly isolated cells seem to be a powerful preparation to study the properties and regulation of ion conductances of rat CCD with several electrophysiological methods. These freshly isolated CCD cells maintain the conductance properties known from principal cells of the intact CCD. 相似文献
4.
Manganese, iron and lipid interactions in rats 总被引:1,自引:0,他引:1
The interactive effects of manganese, iron and lipid on mineral status, manganese-dependent superoxide dismutase (MnSOD) activity and lipoprotein composition were investigated by feeding weanling rats two levels of manganese (0.4 or 56 micrograms Mn/g diet), two levels of iron (29 or 109 micrograms Fe/g diet) and either 12% high-linoleic acid safflower oil or 12% high-oleic acid safflower oil for 8 wk. Rats fed the manganese-deficient diets had decreased heart MnSOD activity; depressed tibia and kidney manganese concentrations; lowered plasma and high density lipoprotein (HDL) cholesterol, HDL protein and HDL apo E concentrations; and elevated HDL protein/cholesterol ratios. Ingestion of supplemental iron slightly decreased heart MnSOD activity and tibia and kidney manganese concentrations but had no effect on hematocrits or on plasma and HDL cholesterol levels. Rats fed the linoleic acid-rich rather than the oleic acid-rich oil had increased heart MnSOD activity but had unchanged plasma and HDL cholesterol levels. The decrease in plasma and HDL cholesterol levels with manganese deficiency appeared not to be a result of increased lipid peroxidation but may have resulted from decreased cholesterol synthesis and/or secretion. 相似文献
5.
Keith D. Allen William J. Warzak Nancy G. Greger Toni D. Bernotas Carol A. Huseman 《Children's Health Care》1993,22(1):61-72
Fifty-six children with isolated growth hormone deficiency (IGHD) and their families completed self-report instruments about behavioral, social, and emotional adjustment of the children. Results show that children with IGHD may experience significant behavioral and social adjustment problems. Social and emotional adjustment was best predicted by the relative height discrepancy between an individual and their normal-sized peers. Adjustment varied depending on the type of adjustment under consideration, the relative height discrepancy of the individual, the age and gender of the child, and the amount of time in treatment. Discussion addresses the need for an interdisciplinary approach to effective patient management of children with IGHD. 相似文献
6.
M. Köttgen J. Leipziger K. -G. Fischer R. Nitschke R. Greger 《Pflügers Archiv : European journal of physiology》1994,428(2):179-185
The pH regulation in HT29 colon carcinoma cells has been investigated using the pH-sensitive fluorescent indicator 2,7-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF). Under control conditions, intracellular pH (pHi) was 7.21±0.07 (n=22) in HCO
3
–
-containing and 7.21±0.09 (n=12) in HCO
3
–
-free solution. HOE-694 (10 mol/l), a potent inhibitor of the Na+/H+ exchanger, did not affect control pHi. As a means to acidify cells we used the NH
4
+
/NH3 (20 mmol/l) prepulse technique. The mean peak acidification was 0.37±0.07 pH units (n=6). In HCC
3
–
-free solutions recovery from acid load was completely blocked by HOE-694 (1 mol/l), whereas in HCO3
3
–
-containing solutions a combination of HOE-694 and 4,4-diisothiocyanatostilbene-2, 2-disulphonate (DIDS, 0.5 mmol/l) was necessary to show the same effect. Recovery from acid load was Na+-dependent in HCO
3
–
-containing and HCO
3
–
-free solutions. Removal of external Cl– caused a rapid, DIDS-blockable alkalinization of 0.33±0.03 pH units (n=15) and of 0.20±0.006 pH units (n=5), when external Na+ was removed together with Cl–. This alkalinization was faster in HCO
3
–
-containing than in HCO
3
–
-free solutions. The present observations demonstrate three distinct mechanisms of pH regulation in HT29 cells: (a) a Na+/H+ exchanger, (b) a HCO
3
–
/Cl– exchanger and (c) a Na+-dependent HCC
3
–
transporter, probably the Na+-HCO
3
–
/Cl– antiporter. Under HCO
3
–
— free conditions the Na+/H+ exchanger fully accounts for recovery from acid load, whereas in HCO
3
–
-containing solutions this is accomplished by the Na+/H+ exchanger and a Na+-dependent mechanism, which imports HCO
3
–
. Recovery from alkaline load is caused by the HCO
3
–
/Cl– exchanger.This study was supported by DFG Gr 480/10 相似文献
7.
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
8.
R. Nitschke E. Schlatter O. Eidelman H. J. Lang H. C. Englert Z. I. Cabantchik R. Greger 《Pflügers Archiv : European journal of physiology》1989,413(5):559-561
Piretanide blocks the Na+ 2Cl– K+ cotransporter protein in the thick ascending limb (TAL) of the loop of Henle reversibly. When tested from the luminal side in isolated perfused cTAL segments it leads to a half maximal inhibition (IC50) of the equivalent short circuit current (Isc) at a concentration of 10–6 mol/l. From the basolateral side it has no effect on Isc up to 10–4 mol/l. The present study was designed to search for high affinity blockers of the Na+ 2Cl– K+ cotransporter with large molecular weight in an attempt to use these macromolecules for antibody-labelling or affinity separation of this transport-protein. Amino-ethyl-dextran or amino-ethyl-polyethylene glycol (M.W. 5kd) were coupled to isothiocyanato-piretanide (ISO-PIR) at room temperature in DMSO. The resulting compounds dextran-sulfonylurea-piretanide (PIR-DEX) and polyethylene glycol-sulfonylurea-piretanide (PIR-PEG) (M.W. 5.38kd) were purified and tested in isolated perfused cTAL segments. IC50 values for ISO-PIR, PIR-DEX and PIR-PEG were estimated from dose response curves after their addition to the lumen or bath perfusate, respectively. ISO-PIR, PIR-DEX and PIR-PEG acted from the lumen side at 3·10–6, 6·10–6 and 2·10–6 mol/l. The inhibitory effect was easily reversible. From the basolateral side no effect for any compound was seen at up to 10–4 mol/l. In clearance experiments PIR-DEX was given to female Wistar rats as an i.v. bolus (25 mol/kg) and the diuretic urine was collected. After dialysis (exclusion limit 2.5kd) the dialysed urine and the dialysate were tested in isolated perfused cTAL segments. The dialysates had no effect on Isc, but the dialysed urine inhibited Isc by 35% from the luminal side. The present data show: High molecular derivatives of piretanide with dextran or polyethylene glycol moieties block the Na+ 2Cl– K+ cotransporter in cTAL segments at roughly the same low concentration as piretanide itself. Our data exclude a metabolism of these piretanide compounds in the kidney. Since these macromolecular probes can probably not enter the cell their inhibitory effect indicates that the binding site for piretanide diuretics on the Na+ 2Cl– K+ cotransporter is exposed on the surface of the luminal cell membrane.This study was supported by Deutsche Forschungsgemeinschaft Gr 480/9 相似文献
9.
Bleich M Hug MJ Heitzmann D Warth R Greger R 《Pflügers Archiv : European journal of physiology》1999,439(1-2):49-51
Previously we have shown that stimulation of in vitro perfused rectal gland tubules (RGT) of the dog-fish Squalus acanthias by adenosine 3',5'-cyclic monophosphate (cAMP), (as a cocktail comprising 0.1 mmol/l dibutyryl-cAMP, 10 micromol/l forskolin and 0.1 mmol/l adenosine, hereafter termed STIM) leads to an increase in cytosolic Ca2+ ([Ca2+]i) and that this assists Cl- secretion by enhancing basolateral K+ conductance. In the present study we examined the mechanism of the cAMP-induced increase in [Ca2+]i. [Ca2+]i was measured using the fura-2 technique in isolated in vitro perfused RGT. As before, STIM enhanced [Ca2+]i. This elevation of [Ca2+]i was prevented completely when STIM was added in the presence of the Na+2Cl-K+ cotransport inhibitor furosemide (0.5 mmol/l). This suggests that the increase in [Ca2+]i induced by STIM is caused by a concomitant increase in cytosolic Na+ ([Na+]i) and not by the activation of second messenger cascades. Furosemide prevents this increase in [Na+]i and hence the elevation of [Ca2+]i. Moreover, the plateau phase of the [Ca2+]i transient produced by carbachol (CCH, 0.1 mmol/l) was augmented strongly when bath Na+ was reduced to 5 mmol/l. These data suggest that the level of [Ca2+]i is determined by Na(+)-dependent Ca2+ export, most likely via a Na+/Ca2+ exchanger. The increase in [Na+]i accompanying stimulation of Cl- secretion reduces the rate of Ca2+ export leading to an elevation of [Ca2+]i, as does a reduction in bath Na+ which augments the [Ca2+]i plateau produced by CCH. 相似文献
10.
Properties and regulation of chloride channels in cystic fibrosis and normal airway cells 总被引:4,自引:0,他引:4
Karl Kunzelmann Hermann Pavenstädt Rainer Greger 《Pflügers Archiv : European journal of physiology》1989,415(2):172-182
The present study examines the properties of Cl–channels in cultured respiratory cells of cystic fibrosis (CF) patients and normal (N) individuals. In excised membrane patches the conductances for CF and N Cl– channels were larger at positive as compared to negative clamp voltages (V
c): 74±2.6 (V
c > 0) and 47±2.0 pS (V
c < 0) for CF (n= 57) and 69±3.6 (V
c > 0) and 45±2.3 pS (V
c < 0) for N (n=35). The open probability (P
o) of the channel increased markedly with depolarization. Both the voltage dependence of the conductance and of P
o contribute to the outward rectification of the channel. The time histogram analysis reveals two open and two closed time constants. The selectivity of the channel was Cl–=Br– =I– > NO
3
–
gluconate. The channel was inhibited reversibly by 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) at 10–7 mol/l to 10–5 mol/l. While Cl– channels were present in cell attached patches of N cells, they were absent in those of CF cells. The mean conductance for cell attached (N) Cl– channels was 76±3.2 pS for positive clamp voltages (V
c) and 46±3.9 pS for negative V
c (n=8). When the membrane patches were excised from CF cells Cl– currents appeared spontaneously (n=19). The immediate appearance (within 1 s) of Cl– channels after excision was observed at positive (n=6) as well as at negative clamp voltage (n=13). Excision activation of CF Cl– channels was observed at low (< 10–9 mol/l) or high (10–3 mol/l) calcium activities on the cytosolic side of the excised patch. Variation of the Ca+ activity (< 10–9–10–3 mol/l) or pH (6.5–8.5) on the cytosolic side exerted no effects on these Cl– channels. These results suggest that Cl– channels are present in the apical membrane of CF and N respiratory cells but they seem to be inhibited in intact CF cells. Excision of the patch and hence removal of the cytosolic inhibitor leads to an activation of Cl– channels. The Cl– channels in excised patches of N and CF cells have identical properties. 相似文献