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91.
Activation of factor X by both the unactivated tissue factor:factor VII complex (TF:VII) and the activated tissue factor:factor VIIa complex (TF:VIIa) has been studied in the presence of tissue factor pathway inhibitor (TFPI), antithrombin III (ATIII), and heparin. At near-plasma concentrations of TFPI, ATIII, and factor X, factor X activation that occurs in response to TF:VII is essentially abolished in the presence of heparin (0.5 micromol/L). This effect requires both inhibitors, acting on different targets: (1) ATIII, which in the presence of heparin blocks the activation of TF:VII, and (2) TFPI, which inhibits the TF:VIIa that is generated. In the absence of ATIII, TFPI alone with heparin reduces but does not abolish factor X activation. Conversely, in the absence of TFPI, ATIII + heparin reduces but does not abolish TF:VIIa generation and allows continuing activation of factor X. These results indicated that when the unactivated TF:VII complex is the initiating stimulus, heparin-dependent reduction in the rate and extent of factor X activation requires both ATIII and TFPI. In contrast, if TF:VIIa is used to initiate activation, only TFPI is involved in its regulation. 相似文献
92.
K E Stewien L C da Cunha A de C Alvim S A dos Reis Filho M A Alvim A A Brand?o M N Neiva 《Revista do Instituto de Medicina Tropical de S?o Paulo》1991,33(6):459-464
A total of 479 diarrhoeic children and 337 children without diarrhoea (controls) less than 5 years old were investigated in a two-year study in the city of S. Luís (MA), with the purpose to determine the incidence, the age distribution and the seasonality of rotaviruses, as well as to establish the severity of the disease in this region between the North and the Northeast of Brazil. rotavirus incidence was highest in children of the 1st. year of life, showing an average of 25% per year among the diarrhoeic patients attending the two main hospitals and three health units at the periphery of the city. It was shown that rotaviruses are significant enteropathogens in children less than 18 months old. Frequency of rotaviruses dropped in diarrhoeic patients 18 to 23 months old to only 4%, the same percentage observed in children of the control group. A typical seasonal distribution of rotaviruses was not seen during the two years of study. There was a peak in the incidence of rotaviruses in 1986, during the rainy season, and two peaks in 1987, one in the rainy season and one in the dry season. It was also shown that severity of diarrhoea in rotavirus positive cases was higher than in the negative cases. Rotavirus diarrhoeic patients had more loose stools per day, and higher frequencies of vomiting and fever, resulting more often (> 2 times) in moderate or severe dehydration. Finally, it is concluded that the introduction of immunoprophylaxis may reduce significantly the high mortality rates in early childhood observed in S. Luís. 相似文献
93.
Hepatosplenic T-cell lymphoma: a distinct clinicopathologic entity of cytotoxic gamma delta T-cell origin 总被引:7,自引:0,他引:7
Cooke CB; Krenacs L; Stetler-Stevenson M; Greiner TC; Raffeld M; Kingma DW; Abruzzo L; Frantz C; Kaviani M; Jaffe ES 《Blood》1996,88(11):4265-4274
We identified eight cases of T-cell lymphoma with evidence of a gamma delta phenotype over a 13-year period. Seven of these cases conformed to a distinct clinicopathologic entity of hepatosplenic gamma delta T- cell lymphoma. Nearly all of these patients were young adult males (five of seven), with a median age at presentation of 20 years. They presented with marked hepatosplenomegaly, without lymphadenopathy or significant peripheral blood lymphocytosis. Thrombocytopenia was seen in all patients, and five of seven were mildly anemic. The clinical course was aggressive, and despite multiagent chemotherapy, the median survival duration was less than 1 year. The morphologic findings were uniform; a monomorphic population of medium-sized lymphoid cells with moderately clumped chromatin and a rim of pale cytoplasm infiltrated the sinusoids of the spleen, liver, and bone marrow. The cells had a characteristic immunophenotype: CD2+, CD3+, CD4-, CD5-, CD7+, CD16+, CD57-, CD25-, T-cell receptor (TCR)delta +, beta F1-. CD8 was positive in four of seven cases tested, and CD56 was positive in five of six. All cases expressed the cytotoxic granule-associated protein, TIA1, but perforin was detected in only one case. All cases with assessable DNA had a TCR gamma gene rearrangement, and lacked Epstein-Barr virus sequences. Isochromosome 7q was identified in two cases with cytogenetic information. The one case of cutaneous gamma delta T-cell lymphoma differed in its clinical manifestations, histologic appearance, and immunophenotype. We conclude that hepatosplenic gamma delta T-cell lymphoma is a distinct clinicopathologic entity derived from cytotoxic gamma delta T cells, and should be distinguished from other lymphomas of T-cell and natural-killer cell (NK)-like T-cell derivation. 相似文献
94.
95.
DLA-identical bone marrow grafts after low-dose total body irradiation: effects of high-dose corticosteroids and cyclosporine on engraftment 总被引:2,自引:1,他引:2
Yu C; Storb R; Mathey B; Deeg HJ; Schuening FG; Graham TC; Seidel K; Burnett R; Wagner JL; Shulman H 《Blood》1995,86(11):4376-4381
Previous studies found that marrow allografts from DLA-identical littermates resulted in survival of 60% of recipient dogs after an otherwise lethal dose of 450 cGy of total body irradiation (TBI), either because of successful allografts or autologous recovery after rejection of the allografts. Forty percent of dogs died with marrow aplasia after allograft rejection. The current study asked whether allogeneic engraftment could be enhanced and survival improved by treating allograft recipients with high doses of corticosteroids or with cyclosporine (CSP), administered either before or after transplantation. Five dogs in group 1 received corticosteroids beginning on day -5 and ending on day 32 after transplant. The starting dose was 12.5 mg of prednisone per kilogram orally twice daily. All five dogs rejected their allografts; three died early with marrow aplasia and two showed endogenous marrow recovery. Nine dogs received CSP from day -6 to day -1 before transplantation at a dose of 20 mg/kg/d intravenously administered in divided doses. All nine dogs rejected the marrow allograft; six died with marrow aplasia and three survived with endogenous marrow recovery. Seven dogs received CSP after transplantation at a dose of 30 mg/kg/d orally from day -1 to day 35. All seven had sustained allografts (two mixed chimeras and five complete donor-type chimeras) and became healthy long-term survivors without graft-versus-host disease. These results extend previous observations and confirm that grafts of marrow from DLA-identical littermates improved survival of dogs exposed to low but otherwise lethal doses of TBI. Additional therapy with high-dose corticosteroids administered peritransplantation and posttransplantation or CSP administered before transplantation neither enhanced the rate of allogeneic engraftment nor improved survival; however, CSP administered after transplantation resulted in successful allografts and event-free survival in all cases. 相似文献
96.
Nash RA; Schuening FG; Seidel K; Appelbaum FR; Boone T; Deeg HJ; Graham TC; Hackman R; Sullivan-Pepe M; Storb R 《Blood》1994,83(7):1963-1970
Recombinant canine granulocyte-macrophage colony-stimulating factor (rcGM-CSF) was studied in normal dogs and in dogs receiving otherwise lethal total body irradiation (TBI) without marrow transplant. Five normal dogs receiving 25 micrograms/kg of rcGM-CSF by subcutaneous (SC) injection twice daily (BID) for 14 days showed increases in peripheral blood neutrophil counts of three to five times the baseline. Platelet counts decreased during administration of rcGM-CSF to a mean nadir of 52,800. Ten dogs received 400 cGy TBI at 10 cGy/min from two opposing 60Co sources and no marrow graft. Within 2 hours of TBI, rcGM-CSF was begun at a dose of 50 micrograms/kg SC BID for 5 doses and then continued at 25 micrograms/kg SC BID for 21 days. Only 1 of the 10 dogs receiving rcGM-CSF survived with complete and sustained recovery of hematopoiesis. One of 13 historical control dogs survived after 400 cGy with no hematopoietic growth factor or marrow infusion. Results with rcGM-CSF were compared with previous and concurrent data with G-CSF studied in the same model. Of 10 dogs receiving G-CSF, 8 survived with complete and sustained hematopoietic recovery, a significantly better survival than that seen with rcGM-CSF (P = .006). Neutrophil counts were sustained at higher levels after TBI for the first 18 days in the G-CSF group (P < .016) and the neutrophil nadirs were higher. No differences in neutrophil nadirs were noted between the rcGM-CSF and control groups. Dogs treated with rcGM-CSF experienced a more rapid decline of platelet counts than G-CSF-treated or control dogs over the first 18 days (P < .001). The nadir of the platelet count was higher in the control group than in either the G-CSF or rcGM-CSF group and no significant difference was observed between the G-CSF and rcGM-CSF groups. After otherwise lethal TBI (400 cGy) in dogs, rcGM-CSF was not effective in promoting hematopoietic recovery or improving survival. 相似文献
97.
Jansen PM; van der Pouw Kraan TC; de Jong IW; van Mierlo G; Wijdenes J; Chang AA; Aarden LA; Taylor FB Jr.; Hack CE 《Blood》1996,87(12):5144-5151
Interleukin (IL)-12 is thought to be a key factor for the induction of interferon gamma (IFN-gamma), a cytokine essential for the lethal effects of endotoxin. We report here on the release of the nonfunctional subunit of IL-12, p40, as well as biologically active heterodimeric IL-12, p70, after administration of a lethal (n = 5) or sublethal (n = 8) dose of live Escherichia coli to baboons. Remarkably, on lethal challenge, peak levels of p40 were observed at 3 hours that were about twofold lower than those elicited after sublethal challenge (2,813 +/- 515 pg/mL v 4,972 +/- 732 pg/mL, P < .05). This disparity was also observed, although to a lesser extent, for IL-12 p70 antigen, of which maximum levels of 91 +/- 47 pg/mL and 151 +/- 41 pg/mL were measured 6 hours after a lethal or sublethal dose of E coli, respectively. Circulating p70 antigen correlated with IL-12 biologic activity (r = 0.869; P < .001). When comparing lethal to sublethal conditions, lower peak levels of IL-12 on lethal E coli sharply contrasted with higher levels of other proinflammatory cytokines, such as tumor necrosis factor (TNF)-alpha, IL-1beta, IL-6, and IL-8 observed in these animals. Lower IL-12 concentrations in the lethal group may have resulted in part from the enhanced production of IL-10, a known inhibitor of IL-12 synthesis in vitro, as peak levels of this cytokine 3 hours postchallenge inversely correlated with peak levels of IL-12, in particular p40 (r = -0.802; P < .01). Contrary to what might be expected if IFN-gamma were solely induced by IL-12, lethally challenged baboons generated threefold more IFN-gamma at 6 hours than those receiving a sublethal dose (P < .05). Moreover, higher levels of IFN- gamma were associated with lower p40/p70 ratios, suggesting that, in agreement with observations in vitro, IFN-gamma may have preferentially upregulated the release of p70 over p40. These data show that IL-12 is released in experimental septic shock in nonhuman primates and suggest that IL-10 and IFN-gamma are involved in the regulation of this release. Furthermore, this study indicates that the systemic release of IL-12 might be essential, but is not likely sufficient, to promote lethal production of IFN-gamma in sepsis. 相似文献
98.
背景和目的:乳酸水平增高与患者的致病率和病死率显著相关.该研究探讨了在危重患者的早期治疗中,监测乳酸水平是否可以改善患者的预后及其效果.方法:将入住ICU时血乳酸水平≥3.0 mmol/L(3.0 mEq/L)的患者随机分为2组,乳酸组以乳酸水平指导治疗,使患者在最初8h内乳酸水平每2h 下降20%以上;对照组仅有基线乳酸水平,不进行乳酸水平监测. 相似文献
99.
Background: It is well documented that high levels of many airborne pollutants can adversely affect many systems of the human body. The aim of this study was to evaluate the specific impact of ozone (O3) on the worsening of childhood asthma, comparing children living at regions with high and low O3 concentrations (reference site) without the confounding effects of other pollutants. Methods: Pollutant concentrations were monitored and data concerning asthma prevalence were collected through a questionnaire. The studied population consisted of 478 children aged 6–13 years old enrolled in four schools of the municipalities where monitoring was performed. Remote sites were identified with very low concentrations of nitrogen dioxide and volatile organic compounds and high concentrations of O3. Results: The prevalence of wheeze for lifetime period and in the past year was 15.9% and 6.3%, respectively. Asthmatic children were identified when dyspnoea and wheezing were simultaneously mentioned in the absence of upper respiratory infections; according to that, the lifetime prevalence of asthmatic symptoms at the remote sites was 7.1%. The comparison with other previous studies was difficult because the criteria for analysis are not conveniently established. Conclusion: The prevalence of childhood asthmatic symptoms was about 4% higher at the high O3 site than at the low O3 site. 相似文献
100.