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51.
M. Venturini L. Del Mastro Franco Testore Marco Danova Ornella Garrone Claudio Lanfranco Fabio Latini Mario R. Sertoli Rita Lionetto Paola Queirolo Andrea Ardizzoni Riccardo Rosso 《Cancer chemotherapy and pharmacology》1996,38(6):487-494
To verify whether the association of granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO) would
allow both the acceleration and the dose escalation of the cyclophosphamide/epidoxorubicin/5-fluorouracil (CEF) regimen as
first-line therapy in advanced breast cancer patients, we conducted a dose-finding study. Cohorts of three consecutive patients
received cyclophosphamide (Ctx, dose range 800 –1400 mg/m2), epidoxorubicin (Epidx, dose range 70–100 mg/m2), and 5-fluorouracil (5-Fu, 600 mg/m2, fixed dose) given as an intravenous bolus on day 1 every 14 days; GM-CSF at 5 μg/kg given as a subcutaneous injection from
day 4 to day 11; and EPO at 150 IU/kg given as a subcutaneous injection three times a week. In no single patient was any dose
escalation allowed. A total of 14 patients entered the study. At the 4th dose level (Ctx 1400 mg/m2, Epidx 100 mg/m2, 5-Fu 600 mg/m2), two patients had dose-limiting mucositis and one patient developed dose-limiting neutropenia. Therefore, the 3rd cohort
received the maximum tolerated dose, i.e. Ctx at 1200 mg/m2, Epidx at 90 mg/m2, and 5-Fu at 600 mg/m2, given every 18.5 (±2.5) days. Toxicity was moderate and manageable in an outpatient setting. Only 1 admission at the 4th
dose level was required. Throughout the 4 dose levels there was no toxicity-related death; grade IV leukopenia ranged from
24% to 75% of cycles and grade IV thrombocytopenia ranged from 6% to 8%. No grade IV anemia was recorded. Increasing the doses
of Ctx and Epidx while maintaining a fixed dose of 5-Fu with the support of both EPO and GM-CSF allows safe acceleration and
dose escalation of CEF chemotherapy. Further controlled studies will evaluate the activity and efficacy of this strategy.
Received: 8 October 1995/Accepted: 1 March 1996 相似文献
52.
Passive intestinal permeability in 33 newborn babies was studied using feeds containing lactulose and mannitol. Each marker is thought to pass across the gut wall by a different route; lactulose by a paracellular and mannitol by a transcellular pathway. Neither is metabolised and both are wholly and solely excreted by the kidney; urinary recovery is a measure of the intestinal uptake. Babies born before 34 weeks' gestation exhibited a higher intestinal permeability to lactulose than more mature babies, and all preterm babies showed an appreciable decline in lactulose absorption during the first week of oral feeds. Babies of 34 to 37 weeks' gestation achieved a 'mature' intestinal permeability to lactulose within four days of starting oral feeds. These findings may reflect the immaturity of the gut of the preterm baby rather than a process essential to adaptation to enteral nutrition. 相似文献
53.
Ki-ras mutations are an early event and correlate with tumor stage in transplacentally-induced murine lung tumors 总被引:2,自引:2,他引:2
Leone-Kabler S; Wessner LL; McEntee MF; D'Agostino RB Jr; Miller MS 《Carcinogenesis》1997,18(6):1163-1168
A previous study from this laboratory demonstrated that treatment of
pregnant mice with 3-methylcholanthrene (MC) caused lung tumors in the
offspring at 1 year after birth, the incidence of which correlated with
fetal inducibility of Cyp1a1. Analysis by PCR amplification and allele-
specific hybridization (ASO) of paraffin-embedded tumors generated from
that study revealed the presence of point mutations in exon 1 of the Ki-
ras gene. This work has now been expanded by PCR amplification and ASO
analysis of 31 additional lesions. Point mutations were found in 37 of the
47 (79%) lesions analyzed in this and the previous study, the majority of
which were G-->T transversions in the first or second base of codon 12.
The mutational spectrum appeared to be dependent on the relative stage of
differentiation of the lesion, as both the incidence of mutation and type
of mutation produced correlated with malignant progression. Mutations
occurred in 60% of the hyperplasias, 80% of the adenomas and 100% of the
adenocarcinomas. In the lesions with mutations, GLY12-->CYS12
transversions occurred in 100% of the hyperplasias, 42% of the adenomas and
14% of the adenocarcinomas. The GLY12-->VAL12 transversions occurred in
none of the hyperplasias, 42% of the adenomas and 57% of the
adenocarcinomas. The remaining mutations, which consisted of ASP12
transitions and ARG13 transversions, occurred only in adenomas (17%) and
adenocarcinomas (29%). Between this study and our previous analyses, the
identity of the mutations obtained by ASO were confirmed by sequence
analysis of eight of the 37 lesions that harbored mutations at the Ki-ras
gene locus. There were no differences in the type or incidence of mutations
relative to the metabolic phenotype or sex of the mice. These data suggest
that mutational activation of the Ki-ras gene locus is an early event in
transplacental lung tumorigenesis, and that the type of mutations produced
by exposure to chemical carcinogens can influence the carcinogenic
potential of the tumor. This may have prognostic significance in
determining the malignant progression of the neoplasm.
相似文献
54.
The prevalence of dyslipidaemia in children with insulin dependent diabetes mellitus (IDDM) and its relation to glycaemic control was studied in a group of 51 diabetic children and a control population of 132 schoolchildren. The prevalence of dyslipidaemia in the fasting state was increased in the diabetic group (39%) compared with control subjects (17%). Serum cholesterol concentration alone was raised in 25% of diabetic subjects while serum cholesterol and triglycerides were raised in 14%, compared with 16% and 0.7% respectively in control subjects. Serum total cholesterol (5.1 v 4.5 mmol/l), low density lipoprotein cholesterol (3.2 v 2.6 mmol/l), non-esterified fatty acids (0.91 v 0.50 mmol/l), and triglycerides (0.94 v 0.76 mmol/l) were higher in diabetic children. Serum total cholesterol, triglycerides, and apolipoprotein (apo)B concentrations increased with worsening control, while serum high density lipoprotein cholesterol and apoA-I concentrations were unaltered. There were also positive correlations between glycated haemoglobin and total cholesterol, triglycerides, and apoB in diabetic children. Thus, abnormalities in circulating lipids are common in young subjects with IDDM but largely disappear if blood glucose concentrations are reasonably controlled. 相似文献
55.
56.
57.
In a patient with primary hyperparathyroidism an attempt was made to ablate a middle mediastinal parathyroid gland by forceful staining with radiographic contrast material. The gland was stained on two separate occasions, two weeks apart. Both times the serum calcium level temporarily fell to the normal range but reverted to abnormal levels. The patient ultimately required surgery for correction of hypercalcemia. The mechanism of staining and possible reasons for failure as well as potential complications are discussed. 相似文献
58.
A retrospective review of the dynamic CT studies performed in our institution on head and neck lesions, excluding the brain, was carried out. Five basic types of density vs. time curves were obtained. Dynamic CT scanning is valuable in the differential diagnosis, management, and followup of such cases; its usefulness as an imaging modality in diagnosis and followup of hemangiomas is stressed. 相似文献
59.
60.
Corazzi T Leone M Maucci R Corazzi L Gresele P 《The Journal of pharmacology and experimental therapeutics》2005,315(3):1331-1337
Benzoic acid, 2-(acetyl-oxy)-3-[(nitrooxy)methyl]phenyl ester (NCX 4016), a new drug made by an aspirin molecule linked, through a spacer, to a nitric oxide (NO)-donating moiety, is now under clinical testing for the treatment of atherothrombotic conditions. Aspirin exerts its antithrombotic activity by irreversibly inactivating platelet cyclooxygenase (COX)-1. NCX 4016 in vivo undergoes metabolism into deacetylated and/or denitrated metabolites, and it is not known whether NCX 4016 needs to liberate aspirin to inhibit COX-1, or whether it can block it as a whole molecule. The aim of our study was to evaluate the effects of NCX 4016 and its analog or metabolites on platelet COX-1 and whole blood COX-2 and on purified ovine COX (oCOX)-1 and oCOX-2. In particular, we have compared the mechanism by which NCX 4016 inhibits purified oCOX enzymes with that of aspirin using a spectrophotometric assay. All the NCX 4016 derivatives containing acetylsalicylic acid inhibited the activity of oCOX-1 and oCOX-2, whereas the deacetylated metabolites and the nitric oxide-donating moiety were inactive. Dialysis experiments showed that oCOX-1 inhibition by NCX 4016, similar to aspirin, is irreversible. Reversible COX inhibitors (indomethacin) or salicylic acid incubated with the enzyme before NCX 4016 prevent the irreversible inhibition of oCOX-1 by NCX 4016 as well as by aspirin. In conclusion, our data show that NCX 4016 acts as a direct and irreversible inhibitor of COX-1 and that the presence of a spacer and NO-donating moiety in the molecule slows the kinetics of COX-1 inhibition by NCX 4016, compared with aspirin. 相似文献