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1.
L. Porto E. Hattingen U. Pilatus M. Kieslich B. Yan D. Schwabe F. E. Zanella H. Lanfermann 《Child's nervous system》2007,23(3):305-314
Background Diagnosis of brainstem lesions in children based on magnetic resonance imaging alone is a challenging problem. Magnetic resonance
spectroscopy (MRS) is a noninvasive technique for spatial characterization of biochemical markers in tissues and gives information
regarding cell membrane proliferation, neuronal damage, and energy metabolism.
Methods We measured the concentrations of biochemical markers in five children with brainstem lesions and evaluated their potential
diagnostic significance. Images and spectra were acquired on a 1.5-T imager. The concentrations of N-acetylaspartate, tetramethylamines (e.g., choline), creatine, phosphocreatine, lactate, and lipids were measured within lesions
located at the brainstem using Point-resolved spectroscopy sequences.
Results Diagnosis based on localized proton spectroscopy included brainstem glioma, brainstem encephalitis, demyelination, dysmyelination
secondary to neurofibromatosis type 1 (NF 1), and possible infection or radiation necrosis. In all but one patient, diagnosis
was confirmed by biopsy or by clinical follow-up.
Conclusions This small sample of patients suggests that MRS is important in the differential diagnosis between proliferative and nonproliferative
lesions in patients without neurofibromatosis. Unfortunately, in cases of NF 1, MRS can have a rather misdiagnosis role. 相似文献
2.
3.
Martin J. Lohse Bernice Elger Jutta Lindenborn-Fotinos Karl-Norbert Klotz Ulrich Schwabe 《Naunyn-Schmiedeberg's archives of pharmacology》1988,337(1):64-68
Summary Human platelet membranes were solubilized with the zwitterionic detergent CHAPS (3-[3-(cholamidopropyl)dimethylammonio]-1-propanesulfonate) and the solubilized extract subjected to gel filtration. Binding of the adenosine receptor agonist [3H]NECA (5-N-ethylcarboxamidoadeno-sine) was measured to the eluted fractions. Two [3H]NECA binding peaks were eluted, the first of them with the void volume. This first peak represented between 10% and 25% of the [3H]NECA binding activity eluted from the column. It bound [3H]NECA in a reversible, saturable and GTP-dependent manner with an affinity of 46 nmol/1 and a binding capacity of 510 fmol/mg protein. Various adenosine receptor ligands competed for the binding of [3H]NECA to the first peak with a pharmacological profile characteristic for the A2 adenosine receptor as determined from adenylate cyclase experiments. In contrast, most adenosine receptor ligands did not compete for [3H]NECA binding to the second, major peak. These results suggest that a solubilized A2 receptor-GS protein complex of human platelets can be separated from other [3H]NECA binding sites by gel filtration. This allows reliable radioligand binding studies of the A2 adenosine receptor of human platelets.Abbreviations CHAPS
3-[3-(cholamidopropyl)dimethylammoniol-l-propanesulfonate
- CIA
2-chloroadenosine
- CPA
N6-cyclopentyladenosine
- DPX
1,3-diethyl-8-phenylxanthine
- NECA
5-N-ethylcarboxamidoadenosine
- PAA
2-phenylaminoadenosine
- PIA
N6-phenyhsopropyladenosine
- XAC
8-{4-[([{(2-aminoethyl)amino}carbonyl}methyl)oxy]phenyl]-1,3-dipropylxanthine
Send offprint requests to M. J. Lohse 相似文献
4.
Karl-Norbert Klotz Martin J. Lohse Ulrich Schwabe Gloria Cristalli Sauro Vittori Mario Grifantini 《Naunyn-Schmiedeberg's archives of pharmacology》1989,340(6):679-683
Summary The tritiated analogue of 2-chloro-N6-cyclopentyladenosine (CCPA), an adenosine derivative with subnanomolar affinity and a 10000-fold selectivity for A1 adenosine receptors, has been examined as a new agonist radioligand. [3H]CCPA was prepared with a specific radioactivity of 1.58 TBq/mmol (43 Ci/mmol) and bound in a reversible manner to A1 receptors from rat brain membranes with a high affinityK
D-value of 0.2 nmol/l. In the presence of GTP aK
D-value of 13 nmol/l was determined for the low affinity state for agonist binding. Competition of several adenosine receptor agonists and antagonists for [3H]CCPA binding to rat brain membranes confirmed binding to an A1 receptor. Solubilized A1 receptors bound [3H]CCPA with similar affinity for the high affinity state. At solubilized receptors a reduced association rate was observed in the presence of MgCl2, as has been shown for the agonist [3H]N6-phenylisopropyladenosine ([3H]PIA). [3H]CCPA was also used for detection of A1 receptors in rat cardio myocyte membranes, a tissue with a very low receptor density. A KD-value of 0.4 nmol/l and aB
max-value of 16 fmol/ mg protein was determined in these membranes. In human platelet membranes no specific binding of [3H]CCPA was measured at concentrations up to 400 nmol/l, indicating that A2 receptors did not bind [3H]CCPA. Based on the subnanomolar affinity and the high selectivity for A1 receptors [3H]CCPA proved to be a useful agonist radioligand for characterization of A1 adenosine receptors also in tissues with very low receptor density.Abbreviations CHA
N6-cyclopenyadenosine
- CPA
N6-cy-clopentyladen,osine
- CCPA
2-chloro-N6-cyclopentyladenosine
- CCCPA
2-chloro-5-chloro-5-deoxy-N6-cyclopentyladenosine;
- CHAPS
3-[3-(cholamidopropyl)dimethylammonio]-1-propanesulfonate
- DPCPX
8-cyclopentyl-1,3-dipropylxanthine
- NECA
N-ethylcarboxamidoadenosine
- PEI
polyethylenimine
- PIA
N6-phenylisopropyladenosine
Send offprint requests to K.-N. Klotz at the above address 相似文献
5.
Incidence of chromosomal imbalances in advanced colorectal carcinomas and their metastases 总被引:6,自引:0,他引:6
Knösel T Petersen S Schwabe H Schlüns K Stein U Schlag PM Dietel M Petersen I 《Virchows Archiv : an international journal of pathology》2002,440(2):187-194
Comparative genomic hybridization (CGH) was used to screen 54 advanced colon carcinomas. i.e., 24 primary tumors and 30 metastases, for chromosomal alterations. Using a sensitive statistical method for the determination of DNA imbalances and histograms for analysis of the incidence of changes, we identified the DNA over-representation of chromosome 20q as the most common alteration being present in 100% of cases. High incidence deletions were observed on 18q21-18q23 (96%), 4q27-4q28 (96%), 4p14 (87%), 5q21 (81%), 1p21-1p22 (72%), 21q21 (74%), 6q16 (72%), 3p12 (66%), 8p24-8p21 (66%), 9p21 (64%), 11q22 (64%), and 14q13-14q21 (64%). Further frequent over-representation was found on 7q12-7q11.2 (75%), 16p11-16p12 (70%), 19p13 (70%), 9q34 (67%), 19q13 (67%), 13q34 (64%), 13q13 (64%), 17q21 (59%), 22q11 (61%), 8q24 (57%), and 1q21 (57%). Pronounced DNA gains and losses being defined as regions in which the ratio profiles exceeded the values of 1.5 and 0.5, respectively, frequently colocalized with peaks of incidence curve. The use of difference histograms for the comparison of tumor subgroups as well as case-by-case histogram for the analysis of 15 paired tumor samples identified several of the above alterations as relevant for tumor progression and metastasis formation. The study identified additional loci and delineates more precisely those that have been previously reported. For comparative purposes, we have made our primary data (ratio profiles, clinicopathological parameters, histograms) available at the interactive web site http://amba.charite.de/cgh, where the incidence of changes can be determined at individual loci and additional parameters can be applied for the analysis of our CGH results. 相似文献
6.
Yang GC; Croaker D; Zhang AL; Manglick P; Cartmill T; Cass D 《Human molecular genetics》1998,7(6):1047-1052
Lethal white foal syndrome (LWFS) is a congenital anomaly of horses
characterized by a white coat colour and aganglionosis of the bowel, which
is similar to Hirschsprung disease (HSCR). We decided to investigate
possible mutations of the endothelin-B receptor gene ( EDNRB ) in LWFS as
recent studies in mutant rodents and some patients have demonstrated EDNRB
defects. First, we identified a full-length cDNA for horse EDNRB . This
cDNA fragment contained a 1329 bp open reading frame which encoded 443
amino acid residues. The predicted amino acid sequence was 89, 91 and 85%
identical to human, bovine and mouse as well as rat EDNRB respectively, but
only 55% identical to the human, bovine and rat endothelin A receptor
(EDNRA). Secondly, sequence analysis, together with allele-specific PCR and
the amplification- created restriction site (ACRS) technique, revealed a
dinucleotide TC-- >AG mutation, which changed isoleucine to lysine in
the predicted first transmembrane domain of the EDNRB protein. This was
associated with LWFS when homozygous and with the overo phenotype when
heterozygous.
相似文献
7.
Martin J. Lohse Dieter Ukena Ulrich Schwabe 《Naunyn-Schmiedeberg's archives of pharmacology》1985,328(3):310-316
Summary Adenosine has been shown to have negative inotropic, chronotropic and dromotropic effects on the heart. The pharmacological profiles of these effects suggest that they are mediated via Ri (A1) adenosine receptors, but a direct demonstration of these receptors is still missing. In the present study we report direct labelling of these receptors with (-)N6-[125I]-p-hydroxyphenylisopropyladenosine ([125I]HPIA). The radioligand bound in a saturable and reversible manner to a crude membrane preparation, the B
max-value was 30.5 fmol/mg protein and the K
D-value 1.1 nmol/l. A similar affinity of the ligand was obtained in kinetic and competition experiments. Competition experiments with a variety of adenosine analogues gave a pharmacological profile characteristic of Ri adenosine receptors with high affinities of N6-substituted derivatives and a marked stereospecificity for N6-phenylisopropyladenosine (PIA). Purification of the membrane preparation by density gradient centrifugation resulted in a 30-fold increase in the number of binding sites which was paralleled by a similar increase in the number of binding sites for [3H]ouabain. Guanine nucleotides decreased binding of [125I]HPIA in a dose-dependent manner, but the IC50-values were considerably higher than those reported in other tissues. Finally, binding of [125I]HPIA appeared to be entropy-driven which has been shown to be characteristic of agonist binding to Ri adenosine receptors. These results suggest the presence of Ri adenosine receptors in ventricular myocardium which may be responsible for the mediation of the effects of adenosine and its analogues.Abbreviations [125I]HPIA
(-)N6-[125I]-p-hydroxyphenylisopropyladenosine
- (-)IHPIA
(-)N6-iodo-p-hydroxyphenylisopropyladenosine
- (+)/(-)PIA
(+)/(-)N6-phenylisopropyladenosine
- CHA
N6-cyclohexyladenosine
- NECA
5-N-ethylcarboxamidoadenosine
- App(NH)p
5-adenylylimidodiphosphate
- Gpp(NH)p
5-guanylylimidodiphosphate 相似文献
8.
D. Ukena C. G. Schirren K. -N. Klotz U. Schwabe 《Naunyn-Schmiedeberg's archives of pharmacology》1985,331(1):89-95
Summary Adenosine receptors in guinea pig lung were characterized by measurement of cyclic AMP formation and radioligand binding. 5-N-Ethylcarboxamidoadenosine (NECA) increased cyclic AMP levels in lung slices about 4-fold over basal values with an EC50 of 0.32 mol/l. N6-R-(–)-Phenylisopropyladenosine (R-PIA) was 5-fold less potent than NECA. 5-N-Methylcarboxamidoadenosine (MECA) and 2-chloroadenosine had EC50-values of 0.29 and 2.6 mol/l, whereas adenosine and inosine had no effect. The adenosine receptors in guinea pig lung can therefore be classified as A2 receptors. Several xanthine derivatives antagonized the NECA-induced increase in cyclic AMP levels. 1,3-Diethyl-8-phenylxanthine (DPX; K
i 0.14 mol/l) was the most potent analogue, followed by 8-phenyltheophylline (K
i 0.55 mol/l), 3-isobutyl-1-methylxanthine (IBMX; K
i 2.9 mol/l) and theophylline (K
i 8.1 mol/l). In contrast, enprofylline (1 mmol/l) enhanced basal and NECA-stimulated cyclic AMP formation. In addition, we attempted to characterize these receptors in binding studies with [3H]NECA. The K
D for [3H]NECA was 0.25 mol/l and the maximal number of binding sites was 12 pmol/mg protein. In competition experiments MECA (K
i 0.14 mol/l) was the most potent inhibitor of [3H]NECA binding, followed by NECA (K
i 0.19 mol/l) and 2-chloroadenosine (K
i 1.4 mol/l). These results correlate well with the EC50-values for cyclic AMP formation in lung slices. However, the K
i-values of R-PIA and theophylline were 240 and 270 mol/l, and DPX and 8-phenyltheophylline did not compete for [3H]NECA binding sites. Therefore, a complete characterization of A2 adenosine receptors by [3H]NECA binding was not achieved. In conclusion, our results show the presence of adenylate cyclase-coupled A2 adenosine receptors in lung tissue which are antagonized by several xanthines. 相似文献
9.
Martin J. Lohse Sabine Böser Karl-Norbert Klotz Ulrich Schwabe 《Naunyn-Schmiedeberg's archives of pharmacology》1987,336(2):211-217
Summary The effects of barbiturates on the GABA-receptor complex and the A1 adenosine receptor were studied. At the GABA-receptor complex the barbiturates inhibited the binding of [35S]t-butylbicyclophosphorothionate ([35S]TBPT) and enhanced the binding of [3H]diazepam. Kinetic and saturation experiments showed that both effects were allosteric. Whereas all barbiturates caused complete inhibition of [35S]TBPT binding, they showed varying degrees of maximal enhancement of [3H]diazepam binding; (±)methohexital was identified as the most efficacious compound for this enhancement. At the A1 adenosine receptor all barbiturates inhibited the binding of [3H]N6-phenylisopropyladenosine ([3H]PIA) in a competitive manner. The comparison of the effects on [3H]diazepam and [3H]PIA binding showed that excitatory barbiturates interact preferentially with the A1 adenosine receptor, and sedative/anaesthetic barbiturates with the GABA-receptor complex. It is speculated that the interaction with these two receptors might be the basis of the excitatory versus sedative/anaesthetic properties of barbiturates.Abbreviations GABA
-aminobutyric acid
- TBPT
t-butylbicyclophosphorothionate 1073
- DMBB
5-(1,3-dimethyl)butyl-5-ethylbarbituric acid
- MCB
N-methyl-5-(1-cyclohexen-1-yl)-5-ethylbarbituric acid
- MPPB
N-methyl-5-phenyl-5-propylbarbituric acid
- PIA
N6-phenylisopropyladenosine
Send offprint requests to M. J. Lohse at the above address 相似文献
10.
Dirk Martens Martin J. Lohse Bernhard Rauch Ulrich Schwabe 《Naunyn-Schmiedeberg's archives of pharmacology》1987,336(3):342-348
Summary The aim of the present study was the characterization of adenosine receptors in isolated rat ventricular myocytes. The CAMP-levels of rat ventricular myocytes in the presence of 1 mol/l isoprenaline were reduced by up to 48% by adenosine analogues; the rank order of potency was: R-N6-phenylisopropyladenosine (IC50 60 nmol/1), 5-N-ethylcarboxamidoadenosine (IC50 360 nmol/l) and S-N6-phenylisopropyladenosine (IC50 16 ol/l). The adenosine receptor antagonist XAC (xanthine amine congener) antagonized the effect of R-N6-phenylisopropyladenosine in a concentration-dependent manner with a Ki-value of 20 nmol/l. The A1 receptor-selective radioligand R-N6-125I-p-hydroxyphenylisopropyladenosine bound to membranes prepared from rat ventricular myocytes in a saturable manner with a B
max of 17.7 fmol/mg protein and a K
D-value of 1.1 nmol/l. Adenosine analogues competed for the binding with the same rank order of potency as for the inhibition of the isoprenaline-induced cAMP-increase. GTP inhibited radioligand binding with an IC50-value of 73 ol/l. These results suggest the presence of A1 adenosine receptors on rat ventricular myocytes, which mediate an inhibition of adenylate cyclase. The receptors may be responsible for the effects of adenosine and its analogues on the heart.Abbreviations
125I-HPIA
R-N6-125I-p-hydroxyphenylisopropyladenosine
- PIA
N6-phenylisopropyladenosine
- NECA
5-N-ethyl-carboxamidoadenosine
- XAC
8-4-[([(2-aminoethyl)aminocarbonyl]methyl)oxy]phenyl-1,3-dipropylxanthine (xanthine amine congener)
- Ro 20-1724
4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone
- ScAMPTME
2-O-monosuccinyladenosine-3,5-cyclic monophosphate tyrosyl methyl ester
- HEPES
N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid
- GTP
guanosine-5-tri-phosphate
Send offprint requests to D. Martens 相似文献