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91.
The binding and processing of monoclonal human IgG1 by cells of a human macrophage-like cell line (U937) 总被引:2,自引:0,他引:2
The goal of these experiments was to assess the relationship between the binding and processing of IgG by Fc-receptor-bearing cells. Cells of the U937 human macrophage-like cell line were incubated with 125I- labeled monomers, dimers, oligomers (composed of 2-4 IgG1 subunits), and HP (heavy polymers composed of 5 or more subunits per polymer) of monoclonal human IgG1 in vitro. Binding was assessed by spinning cells through a layer of phthalate oils. Internalization of IgG1 was assessed by quantitating residual binding to cells after surface-bound IgG was removed by a brief treatment with a solution containing 0.25 M acetic acid and 0.5 M sodium chloride. Catabolism was assessed by measuring the release of radioactive fragments of IgG1, which were not precipitated by 10% trichloroacetic acid. Unstimulated U937 bound about 10,000 molecules per cell of IgG1 monomer, with an equilibrium binding constant (Ka) of 5 X 10(8) M-1. After stimulation with a conditioned medium in vitro, binding per cell was increased 3-7--fold, and the Ka was decreased 2-4--fold. Both unstimulated and stimulated cells internalized and catabolized labeled IgG1 HP, but stimulated cells internalized and digested much more IgG1 HP per cell than unstimulated cells. Both monomers and dimers of IgG1 were internalized and degraded very slowly by stimulated cells, even though both preparations readily bound to cells. In contrast, oligomers and (to an even greater extent) IgG1 HP were internalized and degraded much more rapidly. Internalization of IgG1 HP was markedly inhibited by incubation at 4 degrees C, but not by incubation with a variety of metabolic inhibitors. Catabolism was inhibited by chloroquine and monensin (inhibitors of lysosomal acidification) and by cytochalasin (an inhibitor of microfilament polymerization). Binding to the surface of cells was not markedly inhibited by any agent tested. The capacity of cells to bind labeled IgG1 was markedly reduced by prior incubation in the presence of unlabeled IgG1. This reduction was in part due to the steric blockade of receptors caused by the avid, but reversible, binding of IgG1. In addition, IgG1 oligomers or HP (but not IgG1 monomers or dimers) also caused an irreversible reduction in the number of Fc receptors by a process analogous to receptor down-regulation, as observed in other receptor--ligand systems. 相似文献
92.
A method using gas chromatography with organic nitrogen-sensitive detection is described for measurement of antipyrine and aminopyrine concentrations in biological fluids. The analysis was performed isothermally on 3% SP-2250 DB after alkalinized saliva was extracted into chloroform. Phenacetin served as internal standard. Low oral doses of antipyrine (1.0-1.8 mg/kg) and/or aminopyrine (2 mg/kg) were measured accurately in saliva of normal human subjects. The standard curves for antipyrine and aminopyrine were linear from 0 to 10 microgram/ml. The coefficient of variation, determined at a salivary concentration of 2 microgram/ml, was 1.7% for antipyrine and 2.4% for aminopyrine. Saliva concentrations obtained by this method in normal human subjects after either an oral dose of antipyrine (18 mg/kg) or aminopyrine (9 mg/kg) agreed closely with those determined by the flame ionization gas-chromatographic method used to measure higher concentrations of antipyrine and aminopyrine. Antipyrine (1.8 mg/kg) administered concomitantly with aminopyrine (1 mg/kg or 2 mg/kg) to normal male volunteers prolonged mean saliva antipyrine half-life by about 25-33% compared to values obtained when these same subjects received the same dose of antipyrine alone. 相似文献
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95.
Spontaneous disseminated squirrel fibroma 总被引:1,自引:0,他引:1
96.
Madhotra D Fenton JE Makura ZG Charters P Roland NJ 《Irish journal of medical science》2004,173(4):197-199
Background The timing of aggressive airway intervention in adult epiglottitis is controversial.
Aims To correlate Friedman’s staging of epiglottitis on admission with the airway interventions undertaken.
Methods A retrospective study of 23 adult patients, mean age 51 years (range 29–81 years), who had been admitted with acute supraglottitis
between March 1988 and December 2000 was undertaken.
Results Three patients (13%) had airway interventions; two with tracheostomy and one with tracheal intubation. All were Friedman
stage III and had rapid symptom progression during the 24 hours prior to admission. Three other stage III patients with symptom
progression longer than 24 hours and all the remaining patients (stage II or less) were managed with observation and intravenous
therapy.
Conclusions Friedman originally advocated airway intervention in any patient stage II or worse, but this intubation threshold should
probably be lowered to those patients with rapid-onset stage III (moderate respiratory distress, stridor, respiratory rate
>30 per minute, pCO2 >45mmHg) disease. 相似文献
97.
Williams LE Beatty BG Shively JE Beatty JD 《Cancer biotherapy & radiopharmaceuticals》2001,16(2):147-157
A comparison was made between labeled antibody accumulations in nude mice having either single or multiple human xenografts. The LS174T tumors were implanted subcutaneously. All animals were given 2 micrograms of labeled murine anti-carcinoembryonic antigen (CEA) monoclonal antibody 111In-mT84.66. Some animals were also given specific antibody pretreatment (SAP) of 200 micrograms of unlabeled mT84.66 to reduce liver accumulation of activity. In order to represent these multiple tumor examples, a simple initial-phase pharmacokinetic model was first fitted to each of the two groups (SAP and PBS treated) of single-tumor animals. Using the resultant six non-adjustable parameters as constants, the n = 1 uptake model was then used to represent tumor, liver and blood accumulations (%injected dose/organ) in the multiple-tumor animals. The model was found to be a good representation; in particular, it had far better agreement than single tumor predictions in the PBS mice. Differences between the single-tumor accumulations and those seen in multiple tumor examples were generally between two- and three-fold. The model also demonstrated that the result of SAP was to essentially eliminate the effect of liver targeting of tumor-secreted CEA. We conclude that an initial-phase one-tumor model can describe the decrease of accumulation of activity in the case of multiple tumors in nude mice in both untreated (PBS) and pretreated conditions. Implications for clinical imaging and therapy with monoclonal agents are discussed. 相似文献
98.
Williams LE Wu AM Yazaki PJ Liu A Raubitschek AA Shively JE Wong JY 《Cancer biotherapy & radiopharmaceuticals》2001,16(1):25-35
Three analytic indicators were used to compare five members of a monoclonal antibody (Mab) family. The cognates consisted of the genetically engineered intact chimeric IgGI (cT84.66) and related engineered fragments [scFv, diabody, minibody, F(ab')2] reactive against the same epitope of carcinoembryonic antigen (CEA). All analyses were based on radioiodinated Mabs targeting to colorectal xenografts of LS174T tumors in nude mice. Affinity constants were evaluated initially. A second indicator was the imaging figure of merit (IFOM) which determines how rapidly a statistically significant tumor image can be acquired. Finally, deconvolution was used to determine tumor temporal response to an arterial bolus. This last analysis gave the possible tumor accumulation in the absence of normal tissue sequestration. Affinities were all in excess of 10(8) M-1 and were highest for the divalent Mabs. Using the IFOM criterion, an 131I label was best suited as a radiolabel for the intact (IgG) T84.66, while an 123I label indicated optimal imaging with either minibody or F(ab')2. Deconvolution analyses showed that divalent members behaved similarly while the univalent member (scFv) had a tumor residence time smaller by an order of magnitude. The diabody had the largest impulse response function, but renal uptake may limit its present usefulness. 相似文献
99.
AM Pierides HA Ellis H Dellagrammatikas JE Scott AW Norman 《Archives of disease in childhood》1977,52(6):464-472
Three children with azotaemic renal osteodystrophy were treated with 1,25-dihydroxycholecalciferol (1,25(OH)2D3). All showed clinical, biochemical, and radiological improvement within 6 months of starting treatment. There were no complications. The dose of 1,25(OH)2D3 required was 0-5 microgram per day for 2 children aged 22 and 30 months, and 2 microgram per day for a 15-year-old boy. 2 of the patients were receiving phenobarbitone and phenytoin and in one of them prior treatment with dihydrotachysterol 0-5 mg daily and 6 microgram 1alpha-hydroxycholecalciferol (1alphaOHD3) daily had failed to induce improvement. In one patient, in whom serial iliac bone samples were available, 2 microgram 1,25(OH)2D3 resulted in histological improvement in previously severe osteomalacia. 1,25(OH)2D3 appears to be an effective and safe drug in the treatment of uraemic osteodystrophy. 相似文献
100.