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41.
Nitrosocimetidine (NC) is the nitrosated derivative of cimetidine (Tagamet), a p.o. administered drug used widely in the treatment of stomach ulcers. NC is capable of methylating DNA in vitro and in cultured cells in a manner similar to that of the laboratory carcinogens 1-methyl-2-nitro-1-nitrosoguanidine and methylnitrosourea (MNU) and gives positive indications in short-term in vitro tests for genotoxicity, generally held to be prognostic of compound carcinogenic potential. Nevertheless NC has been found to be a weak or non-carcinogen in the rat and mouse model systems and to produce minimal levels of tissue DNA alkylation when dosed p.o. or i.v. to rats. The results from our earlier experiments (D. E. Jensen, Cancer Res., 43: 5258-5267, 1983) indicated that compound denitrosation is the primary fate of NC in the rat and suggested that denitrosation is the blood, mediated by hemoglobin sulfhydryl residues, is perhaps the major detoxification mechanism. We now report that whole blood and hemoglobin isolated from various mammalian species differ in their capacity for NC degradation rate enhancement and for compound denitrosation. The observed whole blood activity in the degradation reaction (rat greater than mouse/guinea pig greater than human/hamster) paralleled the hemoglobin activity. The NC half-life in isolated rat blood, 37 degrees C, was found to be about 2 min and in hamster or human blood 27 min. For reference, the MNU half-life in isolated blood is 8 min. Compound denitrosation accounted for at least 75% of the degradation in rat blood and 40 to 55% in human and hamster blood. Parallel NC denitrosation activity was found in the various hemoglobin preparations. The NC degradation rates in the presence of the several hemoglobin species were roughly proportional to the number of sulfhydryls on the hemoglobin tetramers available for reaction with p-chloromercuribenzoate and approximated the rates observed in solutions containing equivalent concentrations of L-cysteine. The percentage of total decomposition due to compound denitrosation in the presence of rat hemoglobin, 95%, was found to be unique relative to the L-cysteine-mediated reactions (about 35%) and the reactions studied over the pH range 6 through 10, the denitrosation process never accounted for more than 50% of the total degradation. Chemically blocking the sulfhydryls on human hemoglobin using iodoacetamide deleted the NC degradation rate enhancement. We found no evidence for nitrosylhemoglobin formation.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
42.
F W Leung E Slodownik D M Jensen G M Van Deventer P H Guth 《Gastrointestinal endoscopy》1987,33(4):284-288
The reflectance spectrophotometric technique measures an index of mucosal hemoglobin concentration and an index of oxygen saturation by spectral analysis of light reflected from the mucosal surface. Using a commercially available unit, a technique for obtaining reproducible endoscopic measurements with acceptable intraobserver and interobserver variability was developed in the anesthetized dogs. The reflectance spectrophotometric finding that experimentally induced prehepatic portal hypertension did not affect gastric mucosal blood flow was confirmed by hydrogen gas clearance measurements. Endoscopic studies in patients with active duodenal ulcer disease revealed a higher index of mucosal hemoglobin concentration and a normal index of oxygen saturation (i.e., an increase in blood flow) at the margin of the ulcer compared with the adjacent normal appearing mucosa. 相似文献
43.
Age and immune response to a surgical stress 总被引:2,自引:0,他引:2
We studied the effects of age and a relatively standardized stress (elective inguinal herniorrhaphy) on immune response. The patients included 20 men, ten at least 60 years old and ten younger, who were free of infection and illness and had not had prior surgery. Immune responses were measured one day before and five and 30 days after operation. We determined immunoglobulin levels, performed three delayed-hypersensitivity skin tests and a test for neutrophil chemotaxis, and measured lymphocyte responses to autologous cells, phytohemagglutinin-P (PHA), concanavalin A (Con A), and pokeweed. We also studied responses in 40 controls matched for age and sex. The responses to PHA and Con A were significantly lower in older patients than in controls at five days after operation; responses to Con A were still significantly lower at 30 days. Morbidity correlated with depressed immune responses in both age groups, even when there was no difference between older and younger patients. 相似文献
44.
d-Amphetamine, 4-OH amphetamine, and epinephrine have been shown in many behavioral studies to facilitate memory when given post-training. The effect of these drugs on the maintained discharge of cells in the locus coeruleus (LC) was investigated using a route of administration (intraperitoneal) and a log-dose range of these drugs comparable to those used in the behavioral experiments.d-Amphetamine profoundly suppressed maintained discharge: an inhibitory effect was observed at every dose (0.1, 1.0, 10.0 mg/kg). In contrast, only the highest dose of 4-OH amphetamine (8.2 mg/kg) inhibited activity in the LC, and this effect was a modest one. Unlike the amphetamines, epinephrine (500 μ/kg) elevated maintained discharge. These results are discussed in the contex of the hypothesized involvement of the LC in the enhancement of memory by these drugs. 相似文献
45.
Early operation or conservative management of patients with small bowel obstruction? 总被引:3,自引:0,他引:3
OBJECTIVE: To evaluate the outcome after initial non-operative treatment in patients with small bowel obstruction (SBO). DESIGN: Prospective study. SETTING: University hospital, Norway. PATIENTS: One hundred and fifty-four patients with 166 episodes of SBO admitted during the period (1994-1995). Patients younger than 10 years as well as patients with large bowel obstruction, paralytic ileus, incarcerated hernia or SBO caused by cancer were excluded from the study. INTERVENTIONS: Patients with signs of strangulation were operated on early. The rest were given a trial of conservative treatment. MAIN OUTCOME MEASURES: Need of operative treatment. Incidence of bowel strangulation, complications and death. RESULTS: There were 166 cases of SBO. Twenty patients were operated on early among whom bowel was strangulated in 9. Among the 146 patients initially treated conservatively 93 (64%) settled without operation, 9 (6%) had strangulated bowel and 3 (2%) died. Of the 91 patients with partial obstruction but no sign of strangulation, 72 (79%) resolved on conservative treatment. CONCLUSIONS: Patients with partial obstruction with no sign of strangulation should initially be treated conservatively. When complete obstruction is present, it may settle on conservative management, but the use of supplementary diagnostic tools might be desirable to find the patients who will need early operative treatment. 相似文献
46.
Removal of prescribed ultrafiltration volumes in hemodialysis requires knowledge of both the ultrafiltration coefficient of the dialyzer and the average transmembrane pressure (TMP) in the dialyzer. While it has been a fairly common practice to assume that the TMP is constant along the length of the dialyzer, it actually decreases linearly from a maximum value at the blood inlet to a minimum value at the blood outlet. In the past, ignoring the difference between arterial and venous TMPs when calculating the dialysate pressure setting did not result in significant errors in ultrafiltration volume. However, with the introduction of erythropoietin therapy and the trend toward high-efficiency dialysis, increases in hematocrit and blood flow rate have led to axial variations in TMP which, if ignored, can lead to inaccurate fluid removal. The goals of this paper are to provide an understanding of how high hematocrits and high blood flow rates affect TMP and ultrafiltration rate, and to provide simple guidelines for ensuring accurate fluid removal. Sample calculations are given on the last page for easy reference. 相似文献
47.
S. Kølvraa J. Koch N. Gregersen P. K. A. Jensen A. L. Jørgensen K. B. Petersen K. Rasmussen L. Bolund 《Clinical genetics》1991,39(4):278-286
Two cloned DNA fragments, one derived from an alpha satellite subfamily common to chromosomes 13 and 21, and the other derived from a similar subfamily common to chromosomes 14 and 22, have been used as biotinylated probes in in situ hybridization studies. Under high stringency conditions, chromosome specific centromeric labelling can be obtained. The applications of this technique in clinical situations are illustrated on metaphases from a fetus with trisomy 21, a fetus with trisomy 13, and a child with clinical features of cat-eye syndrome. 相似文献
48.
L L Christrup J Bonde S N Rasmussen J M Sonnergaard B H Jensen 《Pharmacology & toxicology》1992,71(4):305-307
Single-dose and steady state pharmacokinetics of diltiazem administered in two different oral formulations were assessed with particular reference to rate and extent of absorption. Following single dose administration a significant difference in tmax was observed (2.9 +/- 1.9 and 6.8 +/- 2.6 hr respectively) whereas differences in AUC, t1/2 and Cmax were not significant. The AUC (mean +/- S.D.) values following single dose administration of Cardil and Cardizem were 678.4 +/- 321.5 and 948.6 +/- 580.6 ng.ml-1.hr respectively. The mean and the 95% confidence limits for the observed ratio AUCCardil/AUCCardizem are 0.89 and 0.44-1.34 respectively. At steady-state a significant difference between Cmax/Cmin and tmax was seen Cmax/Cmin being 4.9 and 3.2 respectively and Tmax being 2.7 +/- 2.0 and 6.0 +/- 2.8 hr respectively, whereas Cmax and AUC did not differ significantly. The AUC (mean +/- S.D.) values in steady state of Cardil and Cardizem were 880.1 +/- 399.8 and 1056.8 +/- 509.8 ng.ml-1.hr respectively. The mean and the 95% confidence limits for the observed ratio AUCCardil/AUCCardizem are 0.96 and 0.66-1.26 respectively. Although the observed ratios AUCCardil/AUCCardizem in both the single-dose and the steady-state study do not differ significantly from 1.0, the confidence limits exceed the acceptable values given by Poulsen & Juul (personal communication 1990) (a 20% decrease or increase of the ratio to 0.8 or 1.2). 相似文献
49.
A. Larsson Ch. Jensen M. Bilting S. Ekholm H. Stephensen C. Wikkelsö 《Acta neurochirurgica》1992,117(1-2):15-22
Summary Thirteen patients with normal pressure hydrocephalus were operated upon with an externally manoeuvrable shunt system (Sophy SU8) in order to investigate its influence on clinical outcome, intracranial pressure and cranial CT parameters. The opening pressure was set at high at surgery and lowered stepwise at intervals of three months to medium and low. The clinical condition, intracranial pressure and cranial CT parameters were examined at the end of the 3 months interval on each pressure level.The patients improved within the first 3 months inspite of an unchanged mean intracranial pressure and remained in a stable clinical condition during the rest of the study period. The intracranial pressure was significantly reduced at 9 months. The ventricular index, Evans index, temporal horn and third ventricle width were reduced 3 months post-operatively and did not change significantly during the rest of the study. The pre-operative third ventricle width was correlated to high psychometric test results after shunt surgery. Reduction in ventricular index, Evans index and third ventricle width after surgery correlated to improvement in psychometric scoring.The clinical improvement after shunt surgery for normal pressure hydrocephalus is seen within 3 months and is independent of the adjusted valve pressure. 相似文献
50.
Summary Intracranial haemorrhage due to rupture of an arteriovenous malformation (AVM) during pregnancy is a rare but serious condition that warrants prompt recognition. Once the diagnosis is made, the management is primarily based on neurosurgical rather than obstetric considerations. Due to its rarity, no definitive guidelines exist, and the best time to perform elective surgery (i.e., at presentation or at completion of the pregnancy) is ill-defined. This report describes three patients recently treated at our institution who had AVMs that ruptured during pregnancy. These cases well summarize the difficulties encountered in treating such patients. The diagnostic as well as the therapeutic implications of this condition are discussed. 相似文献