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31.
SHIGEO NAKAMURA SHINYA WAKUSAWA KAZUO TAJIMA KEN-ICHI MIYAMOTO MASATOSHI HAGIWARA HIROYOSHI HIDAKA 《The Journal of pharmacy and pharmacology》1993,45(4):268-273
Abstract— The effects of eight isoquinolinesulphonamide compounds on resistance to vinblastine in adriamycin-resistant mouse leukaemia cells (P388/ADR) which overexpress the relative molecular weight (Mr) 140 kDa P-glycoprotein in the plasma membrane were investigated. N-[2-(Methylamino)ethyl]-5-isoquinolinesulphonamide (H-8) and N-(2-aminoethyl)-5-isoquinolinesulphonamide (H-9) did not reverse vinblastine resistance. N-[2-[N-[3-(4-Chlorophenyl)-2-propenyl]amino]ethyl]-5-isoquinolinesulphonamide (H-86) and N-[2-[N-[3-(4-chlorophenyl)-1-methyl-2-propenyl]amino]ethyl]-5-isoquinolinesulphonamide (H-87) caused accumulation of intracellular vinblastine and inhibition of vinblastine efflux from the cells and reversed the resistance. Addition of an aminoethyl group to the nitrogen atom of the sulphonamide group (W-66) or a formyl group at the terminal amino group (H-85) of H-86 reduced those activities. Conversion of the chlorophenyl group of H-87 to pyridinyl (H-31) or furanyl (H-34) markedly decreased activities against the drug resistance. The activity against vinblastine accumulation closely correlated with the apparent partition coefficient of compounds. These compounds dose-dependently inhibited photoaffinity labelling of a photosensitive analogue of vinblastine, N-(p-azido-(3-[125I])salicyl)-N′-β-aminoethylvindesine ([125I]NASV), and there was a good correlation between inhibition of [125I]NASV-photolabelling and hydrophobicity. Although these isoquinolinesulphonamides inhibited protein kinase A with different magnitudes, this activity did not correlate with the effect on the drug resistance. These results indicate that isoquinolinesulphonamide compounds with a hydrophobic group interact with antitumour drugs on P-glycoprotein and reverse multidrug resistance without involvement of their activity on protein kinase A. 相似文献
32.
Akihiko ENDO Yuko JIN Ken MASUNAGA Masami SHIMADA Yukihiko FUJITA Michiyoshi MINATO Masaaki TAKADA Shigeru TAKAHASHI Kensuke HARADA 《Congenital anomalies》1995,35(3):285-292
ABSTRACT Marshall-Smith syndrome is a rare disorder characterized by accelerated skeletal maturation, bullet-shaped proximal and middle phalanges, dysmorphic facial features, and failure to thrive, and is often associated with mental retardation of variable degree. We describe an 8-month-old female with this syndrome, who has a hypoplastic corpus callosum and extreme upper airway obstruction requiring tracheostomy. Also, we review the previous reports of this syndrome since 1971 (Marshall et al., 1971). 相似文献
33.
Bobkov ANDREY A. Sutoh KAZUO Reisler EMIL 《Journal of muscle research and cell motility》1997,18(5):563-571
Nucleotide and actin binding properties of the truncated myosin head (S1dC) from Dictyostelium myosin II were studied in solution
using rabbit skeletal myosin subfragment 1 as a reference material. S1dC and subfragment 1 had similar affinities for ADP
analogues, ɛADP and TNP-ADP. The complexes of ɛADP and BeFx or AlF4
- were less stable with S1dC than with subfragment 1. Stern-Volmer constants for acrylamide quenching of S1dC complexes with
ɛADP, ɛADP·AlF
4
-
and ɛADP.BeFx were 2.6, 2.9 and 2.2 M-1, respectively. The corresponding values for subfragment 1 were 2.6, 1.5 and 1.1 M-1. The environment of the nucleotide binding site was probed by using a hydrophobic fluorescent probe, PPBA. PPBA was a competitive
inhibitor of S1dC Ca2+-ATPase (Ki = 1.6 μm). The binding of nucleotides to subfragment 1 enhanced PPBA fluorescence and caused blue shifts in the wavelength
of its maximum emission in the order: ATP ≈ ADP·AlF4- ≈ ADP·BeFx > ATPSγS > ADP > PPi. In the case of S1dC, the effects of different nucleotides were smaller and indistinguishable from each other. S1dC bound
actin tighter than S1 (Kd = 7 nm and 60 nm, respectively). The actin activated MgATPase activity of S1dC varied between preparations, and the Vmax and Km values ranged between 3 and 7 s-1 and 60 and 190 μm, respectively. S1dC showed lower structural stability than S1 as revealed by their thermal inactivations
at 35° C. These results show that the nucleotide and actin binding of S1dC and subfragment 1 are similar but there are some
differences in nucleotide and phosphate analogue-induced changes and the communication between the nucleotide and actin binding
sites in these proteins
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
34.
Cyclophosphamide therapy for pure red cell aplasia associated with granular lymphocyte-proliferative disorders 总被引:1,自引:1,他引:0
Granular lymphocytes have been characterized as cells with azurophilic granules in the cytoplasm. Patients with increased numbers of granular lymphocytes are designated as granular lymphocyte-proliferative disorders (GLPDs). A variety of haematological abnormalities are associated with T-cell-lineage GLPD. Among these, pure red cell aplasia is frequent, and adequate therapy is required. Seven patients with pure red cell aplasia, or a related condition complicating T-cell-lineage GLPD, were entered into this study. Cyclophosphamide was initiated at a daily oral dose of 100 mg. After 2 weeks the dose was reduced to 50 mg/d, and maintained at that dose. Cyclophosphamide was administered until the lymphocyte count was <1 ×109 l and T-cell receptor-β gene analysis was used to monitor the response to treatment. All the patients were successfully treated, irrespective of their former treatment. Clinical remission was associated with the disappearance of the abnormal granular lymphocyte clone, as detected by Southern blot hybridization analysis. Therapeutic responses began after 8 weeks, and clinical complete remissions were obtained after 6 months. Oral cyclophosphamide monotherapy can successfully treat the pure red cell aplasia associated with T-cell-lineage GLPD. 相似文献
35.
TOSHIYUKI ISHIKAWA KAZUO KIMURA NAOMICHI MIYAZAKI OSAMU TOCHIKUBO TAKASHI USUI MASANOBU KASHIWAGI MASAO ISHII 《Pacing and clinical electrophysiology : PACE》1992,15(11):1927-1931
Diastolic mitral regurgitation has been observed in patients with DDD pacemakers when the atrioventricular (AV) delay was prolonged. However, diastolic mitral regurgitation associated with first-degree AV block has not been fully studied. We examined transmitral blood flow in 24 patients with first-degree AV block and normal cardiac function (ages 35.3 ± 17.4 years), and in nine patients with DDD pacemakers and normal cardiac function (ages 73.1 ± 8.1 years), using pulsed Doppler echocardiography. Diastolic mitral regurgitation was observed in 19 of 24 patients with first-degree AV block. Although PQ interval was shortened from 0.32 ± 0.06 to 0.20 ± 0.05 seconds (P < 0.01) after 1 mg atropine sulfate IV, the interval between P wave (ECG) and the beginning of diastolic mitral regurgitation did not change, while the duration of diastolic mitral regurgitation was shortened from 0.15 ± 0.03 to 0.05 ± 0.03 seconds (P < 0.01). There was a significant correlation between changes in PQ interval and changes in the duration of diastolic mitral regurgifation (r = 0.92, P < 0.001). Although cardiac output (3.9 ± 0.05 L/min) and pulmonary capillary wedge pressure (5.1 ± 1.5 mmHg) were normal in all patients with pacemakers, diastolic mitral regurgitation was observed when the AV delay was prolonged. The critical PQ interval for the appearance of diastolic mitral regurgitation was 0.23 ± 0.01 seconds. In patients with prolonged PQ intervals, delayed ventricular contraction following atrial contraction may be associated with mitral regurgitation in the presence of a reversed AV pressure gradient. The results of this study suggest that diastolic mitral regurgitation occurs not only in patients with DDD pacemakers, but also with AAIR pacemakers when the PQ interval is prolonged. The occurrence of diastolic mitral regurgitation is associated with the pacing mode or the setting of AV delay. 相似文献
36.
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38.
Short collagenous peptides cross-linked at their amino and carboxy termini with Lys-Lys-dimer template(s) were synthesized, and the effect of the cross-linking on their stabilities was investigated by thermal denaturation experiments. Two chemoselective ligations were used for the construction of the amino and the carboxy cross-linked peptides. The thermal transition temperature (Tm) and the standard free energies (ΔG°) of the cross-linked collagenous peptides increased, and the thermal stabilization effect corresponded to an elongation by two units of the Gly-Pro-Hyp triad. The van't Hoff enthalpy (ΔH°) and the entropy (ΔS°) values of the cross-linked peptides increased with chain elongation, although the increments were smaller than those of the linear peptides. When the same chain lengths were compared, the ΔH° was increased and the ΔS° was nearly the same or increased by the cross-linking. These results suggest that the cross-linking of the collagenous peptides with the Lys-Lys-dimer template(s) for stabilization contributes to the enthalpic effect, rather than the entropic effect. 相似文献
39.
HITOSHI TAKE KAZUO KUBOTA KOUSEI TAMURA HITOSHI KURABAYASHI JUN'ICHI TAMURA TAKUO SHIRAKURA 《Journal of internal medicine》1995,238(3):289-292
Abstract. A 38-year-old Japanese woman was hospitalized for susceptibility to respiratory tract infections. Clinical examinations revealed asymptomatic primary cholestasis, abnormally elevated immunoglobulin M (IgM) and antimitochondrial antibody, being consistent with asymptomatic primary biliary cirrhosis. Three years later her serum immunoglobulin G (IgG) decreased remarkably, whereas other immunoglobulins were unchanged. Immunological examinations on the peripheral blood lymphocytes demonstrated spontaneous over-synthesis of serum IgM and decreased synthesis of IgG due to abnormal function of both T and B cells. Our case suggests a new possible association between primary biliary cirrhosis and IgG deficiency. 相似文献
40.
Magnetic resonance imaging study of the brain in aged volunteers: T2 high intensity lesions and higher order cortical function 总被引:1,自引:0,他引:1
HIROO KASAHARA md HIDEO YAMADA md MUNEHIKO TANNO md MITSURU KOBAYASHI AKIHIDE KARASAWA md KAZUO ENDO SADANOBU USHIJIMA md 《Psychiatry and clinical neurosciences》1995,49(5-6):273-279
Abstract The aims of the present study were to clarify the findings of magnetic resonance imaging (MRI) in the aging brain, and to relate the MRI findings to higher order cortical function. A total of 118 healthy aged volunteers (41 men, 77 women) underwent cranial MRI electroencephalography (EEG), Benton visual retention test (BVRT) and interview. The subjects had no past history or clinical evidence of cerebrovascular disorder, head trauma or dementia and were living at home without any difficulty. The majority of the subjects have participated in this series of studies since 1982. Using a 1.5 T superconductive MR instrument, T1-weighted, proton density and T2-weighted images were obtained. The MRI data were rated visually by regarding 12 items according to fixed criteria. T2 high signal intensity (T2HSI) lesions were found in 69.5% of subjects, the prevalence of which increased with age. T2HSI lesions were most frequently found in the basal ganglia (61.9%), followed by the thalamus (39.0%), parietal lobe (37.0%), temporal lobe (12.7%) and pons (8.5%). Among these lesions, lacunar infarction showed low signal intensity in T1-weighted images and was found in 24.6% of subjects, the prevalence also increasing with age. These findings, including brain atrophy determined according to similar criteria, were correlated closely with the subjects' age. The results of BVRT showed a close relation with T2HSI, suggesting that T2HSI may influence cognitive function. When the subjects were classified according to the presence of T2HSI, lacunar infarction and EEG abnormalities, brain atrophy was significantly milder in a group of subjects with T2HSI(-), lacunar infarction(-) and normal EEG than in the other groups. This suggests that changes seemingly representing physiological aging may be promoted by another pathological which also exerts influences on higher order cerebral function. 相似文献