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101.
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103.
Serologic studies using four murine monoclonal antibodies specific for the common acute lymphoblastic leukemia antigen (CALLA) and five monoclonal antibodies specific for the gp24 surface antigen indicate that these leukemia-associated antigens are present on cells of comparable tissues in man and in four nonhuman primates. As in man, adherent cell populations obtained from skin, lung, and bone marrow of Macaca fascicularis, M mulatta, M nemestrina, and Papio cynocephalus react with these antibodies. Similarly, granulocytes from both man and these nonhuman primates bind CALLA- and gp24-specific antibodies. Radioimmune precipitation experiments confirm the identity of these antigens. Our studies suggest that nonhuman primates can be used to screen serologic reagents to leukemia-associated antigens for potential toxic effects on normal tissues prior to their use in man. Similarly, nonhuman primates could be employed to assess the possible role of antigen-positive stromal cells in the reconstitution of bone marrow following transplantation. 相似文献
104.
Arruda VR; Pieneman WC; Reitsma PH; Deutz-Terlouw PP; Annichino-Bizzacchi JM; Briet E; Costa FF 《Blood》1995,86(8):3015-3020
The molecular characterization of the mutations in hemophilia A patients is hampered by the large size of the factor VIII gene and the great heterogeneity of mutations. In this study, we have performed a protocol involving multiplex polymerase chain reaction in which 19 exons were amplified in four different combinations followed by nonradioactive single-strand conformational polymorphism (SSCP) to screen for mutations. Southern blotting was used to detect inversion of the factor VIII gene resulting from recombination between copies of the gene A (F8A) located in intron 22 of the factor VIII gene and two copies close telomeric region of X chromosome. Forty-two hemophilia A patients (21 with severe and 21 with mild-to-moderate disease) were studied. The inversion of factor VIII occurred in 13 of 21 patients affected by severe hemophilia A. One patient showed a large extra band in addition to the three bands observed after Southern blotting with the F8A probe. An abnormal electrophoretic pattern of SSCP was detected in 85% and 50% of the patients affected by mild-to-moderate and severe disease, respectively. Sixteen different mutations were identified. Eleven mutations were novel and comprised 9 point mutations and 2 small deletions. This study shows that the methodology used is safe and rapid and has potential for detecting almost all of the genetic defects of the studied hemophilia A patients. 相似文献
105.
Marsh JC; Will AJ; Hows JM; Sartori P; Darbyshire PJ; Williamson PJ; Oscier DG; Dexter TM; Testa NG 《Blood》1992,79(12):3138-3144
We have used the long-term bone marrow culture (LTBMC) system to analyze hematopoiesis in three patients with dyskeratosis congenita (DC), two of whom had aplastic anemia, and the third had a normal blood count (apart from mild macrocytosis) and normal BM cellularity. Hematopoiesis was severely defective in all three patients, as measured by a low incidence of colony-forming cells and a low level of hematopoiesis in LTBMC. The function of the marrow stroma was normal in its ability to support the growth of hematopoietic progenitors from normal marrows seeded onto them in all three cases, but the generation of hematopoietic progenitors from patients marrow cells inoculated onto normal stromas was reduced, thus suggesting the defect to be of stem cell origin. The parents and unaffected brother of one of the families have also been studied in LTBMC and all showed normal hematopoietic and stromal cell function. From this study we speculate that there are some similarities between DC and the defect in the W/Wv mouse. 相似文献
106.
In clonogenic assays of hematopoietic progenitors, high concentrations (4 U/mL) of erythropoietin (epo) reduced the formation of granulocyte- macrophage (GM) colonies and diminished the number of granulocytes formed per culture plate. Fetal progenitors were more sensitive to these effects of epo than were progenitors from adults, displaying these reductions at greater than or equal to 1 U epo/mL. The mechanism was investigated by growing fetal progenitors stimulated by recombinant GM-CSF, in the absence of epo, and when eight-cell clones first appeared, mapping their location, then adding epo, and assessing its effect on the subsequent differentiation of the clones. In the absence of epo, the clones developed exclusively into GM colonies. However, if developing clones were presented with epo, 85% matured into GM colonies, but 15% became multilineage or normoblast colonies. In addition, developing clones that were presented with epo produced colonies that contained fewer neutrophils. These effects of epo on neutrophil generation were observed with each of three varieties of recombinant epo, and also with purified human epo, but were not observed using epo that had been neutralized with rabbit anti-epo antiserum. 相似文献
107.
Cairo MS; Christensen R; Sender LS; Ellis R; Rosenthal J; van de Ven C; Worcester C; Agosti JM 《Blood》1995,86(7):2509-2515
Neonates, especially those of very low birthweight (VLBW), have an increased risk of nosocomial infections secondary to deficiencies in development. We previously demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) production and mRNA expression from stimulated neonatal mononuclear cells are significantly less than that from adult cells. Recombinant murine GM-CSF administration to neonatal rats has resulted in neutrophilia, increased neutrophil production, and increased survival of pups during experimental Staphylococcus aureus sepsis. In the present study, we sought to determine the safety and biologic response of recombinant human (rhu) GM-CSF in VLBW neonates. Twenty VLBW neonates (500 to 1,500 g), aged < 72 hours, were randomized to receive either placebo (n = 5) or rhuGM-CSF at 5.0 micrograms/kg once per day (n = 5), 5.0 micrograms/kg twice per day (n = 5), or 10 micrograms/kg once per day (n = 5) given via 2-hour intravenous infusion for 7 days. Complete blood counts, differential, and platelet counts were obtained, and tibial bone marrow aspirate was performed on day 8. Neutrophil C3bi receptor expression was measured at 0 and 24 hours. GM-CSF levels were measured by a sandwich enzyme-linked immunosorbent assay at 2, 4, 6, 12, and 24 hours after the first dose of rhuGM-CSF. At all doses, rhuGM-CSF was well tolerated, and there was no evidence of grade III or IV toxicity. Within 48 hours of administration, there was a significant increase in the circulating absolute neutrophil count (ANC) at 5.0 micrograms/kg twice per day and 10.0 micrograms/kg once per day, which continued for at least 24 hours after discontinuation of rhuGM-CSF. When the ANC was normalized for each patient's first ANC, there was a significant increase in the ANC on days 6 and 7 at each dose level. By day 7, all tested doses of rhuGM- CSF resulted in an increase in the absolute monocyte count (AMC) compared with placebo-treated neonates. In those receiving rhuGM-CSF 5.0 micrograms/kg twice per day, there was additionally a significant increase in the day 7 and 8 platelet count. Tibial bone marrow aspirates demonstrated a significant increase in the bone marrow neutrophil storage pool (BM NSP) at 5.0 micrograms/kg twice per day and 10.0 micrograms/kg once per day. Neutrophil C3bi receptor expression was significantly increased 24 hours after the first dose of rhuGM-CSF at 5.0 micrograms/kg once per day. The elimination half-life (T1/2) of rhuGM-CSF was 1.4 +/- 0.8 to 3.9 +/- 2.8 hours.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
108.
Molecular characterization of a high A2 beta thalassemia by direct sequencing of single strand enriched amplified genomic DNA 总被引:2,自引:0,他引:2
Two families, one of Anglo-Saxon-Dutch descent, and the other, West Indian black, have an atypical beta thalassemia characterized by an unusually high level of Hb A2 in the heterozygous state. Restriction endonuclease mapping showed a deletion of about 1.35 kilobase (kb) in the 5' region of the beta globin gene. Direct sequencing of a specific region of genomic DNA amplified by a new modification of the polymerase chain reaction defined the deletion to be 1,393 base pairs (bp) and to be the same in both families. The deletion extends from 485 bp 5' to the mRNA CAP site to the middle of the second intervening sequence. This deletion, together with three others previously described that remove the 5' end of the beta gene but leave the delta gene intact, are all associated with unusually high levels of Hb A2 in the heterozygous state. 相似文献
109.
V Varea Calderón L Delgado Carbajal E Camacho Díaz M Estringana Pérez E Alert Casas 《Revista española de enfermedades digestivas》2000,92(3):147-159
OBJECTIVE: altered motility or anatomy of the rectum, anus and perineal floor may lead to symptoms which are unresponsive to routine therapeutic approaches. These disturbances usually lead to constipation, fecal incontinence, or both. Different tests and techniques for evaluating anorectal and perineal disorders, developed in the last two decades, make a better understanding of these disorders possible. This study was designed to evaluate the diagnostic benefits of combining manometry, defecography and anal endosonography in the assessment of patients with anorectal disorders. METHODS: twenty-five children with constipation (with or without soiling), incontinence and/or prolapse underwent anal manometry, defecography and anal endosonography. Group A consisted of 9 children with fecal incontinence, group B consisted of 10 children with constipation with soiling, and group C comprised 6 children with constipation without soiling. RESULTS: in group A resting incontinence was associated with a hypotonic external sphincter in 4 out of 9 patients, 2 of whom had internal anal sphincter thinning. In group B resting incontinence was associated with a hypotonic external sphincter in 8 out of 10 patients, 6 of whom had internal anal sphincter thinning. In group C these associations were not seen in any of the patients. CONCLUSIONS: barium enema is not sufficient for an accurate diagnosis of anorectal disorders. No single test is capable of revealing the type of disease. Anal manometry, defecography and endosonography are complementary procedures in the assessment of this group of disorders. This new approach will improve our knowledge of the pathogenesis of these disorders in children. However, further studies are needed to obtain conclusive evidence. 相似文献
110.
Anti-ischemic effects of atenolol versus nifedipine in patients with coronary artery disease and ambulatory silent ischemia 总被引:1,自引:0,他引:1
P C Deedwania E V Carbajal J R Nelson H Hait 《Journal of the American College of Cardiology》1991,17(4):963-969
The anti-ischemic effects of atenolol and nifedipine were compared in a randomized double-blind crossover manner in 24 patients with stable exertional angina and transient silent ischemia during ambulatory electrocardiographic (ECG) monitoring. Both atenolol and nifedipine were effective (p less than 0.005) in reducing the average number and duration of transient ischemic events, but therapy with atenolol was associated with a significantly greater reduction in the mean number (p less than 0.05) and duration (p less than 0.01) of silent ischemic events. Analyses of the silent ischemic activity during the morning hours revealed that only therapy with atenolol produced a significant reduction in the average duration per patient (139 +/- 54 vs. 1,609 +/- 468 s, p less than 0.01) and in the average duration of silent ischemia per event between 6 AM and 12 noon (62 +/- 21 vs. 208 +/- 24 s, p less than 0.005). There were fewer adverse experiences during therapy with atenolol. These results show that although both atenolol and nifedipine are effective in reducing silent ischemic events, treatment with atenolol is associated with significantly greater efficacy, particularly on the morning surge of silent myocardial ischemia. 相似文献