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41.
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Sharon D Yamamoto H McGee TL Rabe V Szerencsei RT Winkfein RJ Prinsen CF Barnes CS Andreasson S Fishman GA Schnetkamp PP Berson EL Dryja TP 《Investigative ophthalmology & visual science》2002,43(6):1971-1979
PURPOSE: To study the possible involvement of the rod (SLC24A1) and cone (SLC24A2) Na-Ca+K exchanger (NCKX) genes in retinal diseases. METHODS: DNA was collected from unrelated patients with retinal disease, mainly from North America. A human genomic library was screened with the cone NCKX cDNA, and hybridizing clones were sequenced to determine the genomic organization of the SLC24A2 gene. The single-strand conformation polymorphism (SSCP) technique and direct sequencing were used to screen the patients' DNA for mutations in SLC24A1 and SLC24A2. The effect of selected missense changes on protein function was tested by measuring potassium-dependent Na-Ca exchange of the mutant proteins expressed in insect cells. RESULTS: Twenty-seven novel sequence changes were found in the rod NCKX gene, 21 of which are unlikely to be pathogenic, because they did not cosegregate with the disease or did not affect conserved regions of the protein. Of the remaining six, two were frameshift mutations found in one patient each. If translated, these alleles would encode nonfunctional proteins. Three of the six possibly pathogenic mutations were missense changes located in conserved regions, and their protein functions were assayed. Only one (Ile992Thr) had a significantly low level of exchanger function, but it was found in two unrelated patients who were heterozygotes with different retinal diseases, and this mutation could not be unequivocally associated with either disease. The last of the six changes is likely to create a new splice acceptor site. The genomic organization of the cone NCKX gene was determined, and it contained 11 exons with a few splice variants. Fifteen novel sequence changes were identified in the cone exchanger gene in patients with a cone dysfunction or degeneration. Only three of these sequence changes, all missense changes found in heterozygous patients, were considered possibly pathogenic. Functional analysis showed only a slight reduction in the activity of the corresponding mutant proteins. CONCLUSIONS: Although variant alleles of the rod and cone NCKX genes were found, none could be definitively associated with a specific retinal disease. The human phenotype associated with mutant exchanger alleles remains unknown. 相似文献
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Serum CA-125 and inhibin B levels in the prediction of ovarian response to gonadotropin stimulation in in vitro fertilization cycles. 总被引:1,自引:0,他引:1
János Urbancsek Erik E Hauzman Akos Murber Ana R Lagarde Thomas Rabe Zoltán Papp Thomas Strowitzki 《Gynecological endocrinology》2005,21(1):38-44
There is much controversy about the relationship between serum CA-125 levels during in vitro fertilization (IVF) cycles and ovarian function. To evaluate the prognostic value of serum CA-125 and inhibin B measurements in predicting ovarian response to gonadotropin stimulation, we compared the CA-125 and inhibin B levels of poor and normal responders on the first day of ovarian stimulation, on the day of ovulation induction (OI) and at oocyte pick-up. Sixteen patients with poor ovarian response (3 oocytes, serum estradiol (E2) 900 pg/ml at OI) in IVF/intracytoplasmic sperm injection cycles were matched with normal responders (6 oocytes, E2 1800 pg/ml) by age, spontaneous cycle day-3 follicle-stimulating hormone level and cause of infertility. Inhibin B concentrations were significantly lower at all three time points in poor responders, but CA-125 levels were not. No statistically significant correlation was found between CA-125 levels and any of the clinical or laboratory parameters examined. Thus, CA-125 measurements during stimulation are not useful in predicting or identifying poor ovarian response to gonadotropin stimulation in IVF cycles. The lack of difference in CA-125 concentrations between poor and normal responders and lack of correlation with E2 or inhibin B levels suggest that ovarian steroidogenesis and other granulosa cell functions do not influence the production of CA-125. Inhibin B, however, seems to predict ovarian response as early as at the start of stimulation. 相似文献
45.
Intraoperative venous blood sampling to localize a small androgen-producing ovarian tumor. 总被引:1,自引:0,他引:1
Michael K Bohlmann Thomas Rabe Hans-Peter Sinn Thomas Strowitzki Michael Von Wolff 《Gynecological endocrinology》2005,21(3):138-141
BACKGROUND: Among other causes of virilization, ovarian tumors can be the cause of excessive androgen production. We report the case of a Leydig cell tumor of the ovary where diagnostic attempts to localize the source of hyperandrogenism preoperatively failed owing to relatively small tumor size. CASE: A 36-year-old woman presented with clinical signs of severe virilization including progressive balding, increased hirsutism, secondary amenorrhea and enlargement of the clitoris. Extensive work-up included endocrinological tests, pelvic ultrasound, magnetic resonance imaging, chromosomal analysis, norcholesterol scintigraphy and selective venous sampling, without direct localization of the source of hyperandrogenism. Persistently high plasma testosterone prompted an explorative laparotomy. Intraoperative selective blood sampling of the ovarian veins and palpation gave evidence of a right ovarian tumor, which was then removed. Histological examination revealed the presence of a pure Leydig cell tumor. CONCLUSION: Exploratory laparotomy with intraoperative selective blood sampling of the ovarian veins might be a useful approach in patients without accurate preoperative localization of androgen-producing tumors of the ovaries. 相似文献
46.
Zwei placebokontrollierte Interventionsstudien mit kombinierter Hormontherapie hatten eine Diskussion hinsichtlich einer Neubewertung des Nutzen-Risiko-Profils der Hormonersatztherapie ausgelöst, da erhöhte Risiken für Brustkrebs, Herzinfarkte, Thrombosen und Hirninsult berechnet wurden. Bei vorbestehender Disposition müssen diese Risiken stets beachtet werden. Insgesamt sind bei individueller Bilanzierung diese jedoch gegenüber dem erreichbaren Nutzen zu relativieren. Die klassischen Indikationen wie vasovegetative und Urogenitale Beschwerden waren nie angezweifelt worden, die Osteoporoseprävention wurde bestätigt. Auch eine Prävention von kolorektalen Karzinomen scheint möglich. Bei individualisierter, niedrigdosierter, indizierter und kontrollierter Anwendung der Hormonersatztherapie ist davon auszugehen, dass der Nutzen die Risiken überwiegt, insbesondere bei frühem Behandlungsbeginn und bei alleiniger Behandlung mit Östrogenen. So zeigte sich in der WHI-Studie für Frauen unter 60 Jahren nur das bekannte Risiko für Venenthrombosen, die Risiken für Herzinfarkte, Brustkrebs, kolorektale Karzinome und Osteoporose waren um 20–40% reduziert. 相似文献
47.
BACKGROUND: Chlorhexidine is a disinfectant that has been used in skin and mouth washes and as a preservative in some vaginal lubricants. A gel containing 0.25% chlorhexidine gluconate has been found to be effective against Chlamydia trachomatis in vitro and in animal models. Applied vaginally, 5 g of this gel could achieve vaginal fluid concentrations of < or = 1250 microg/ml. GOAL: To test the in vitro activity of chlorhexidine in a gel over a pH range of 4 to 8 in the presence or absence of blood. STUDY DESIGN: Organisms were exposed to chlorhexidine for 30 minutes to 2 hours, and the minimum cidal concentration (MCC) was calculated. RESULTS: The MCC for Neisseria gonorrhoeae was 25 microg/ml at 30 minutes and 12.5 microg/ml at 1 to 2 hours of exposure, whereas the MCC for Trichomonas vaginalis was 1250 microg/ml. Chlorhexidine was more active at pH 8 than pH 4, and less active in the presence of blood. The MCC for Lactobacillus crispatus was 1250 microg/ml at pH 4 and only 125 microg/ml at pH 8. CONCLUSIONS: Based on its in vitro activity, chlorhexidine may be an appropriate topical microbicide for prevention of gonorrhea, but not for prevention of trichomoniasis. This study suggests that the presence of blood and pH affect the activity of chlorhexidine against genital pathogens and commensals. 相似文献
48.
H-J Bangstad K. Dahl-Jørgensen P. Kjæxsgaard K. Mevold KF Hanssen 《Acta paediatrica (Oslo, Norway : 1992)》1993,82(10):857-862
Slightly elevated urinary albumin excretion rate (microalbuminuria) is a marker of early diabetic nephropathy, but it is unclear if the established definition of microalbuminuria (20–200 μg/min) is correct for children and adolescents. We investigated the albumin excretion rate, albumin/creatinine ratio and urinary albumin concentration in 150 healthy schoolchildren and adolescents to (a) obtain a reference value for albumin excretion rate, (b) relate albumin excretion to pubertal stages and (c) evaluate albumin/creatinine ratio and morning albumin concentration as screening methods for elevatcd albumin excretion rate. Albumin concentration was measured by immunoturbidimetry in timed overnight urine samples. The albumin excretion showed a skewed distribution (geometric mean 3.2 μg/min, 95 percentile 15.1 μg/min). In girls, a peak in the albumin excretion rate was found at the pubertal stage 4 (Tanner) and in boys at stage 5. Albumin/creatinine ratio of 2.5 mg/mmol as a scrccning level for elevatcd albumin cxcrction (15 μg/min) showed a high positivc (0.88) and negative (0.99) predictive value. 相似文献
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