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81.
The effect of the Fanconi anemia polypeptide, FAC, upon p53 induction and G2 checkpoint regulation 总被引:3,自引:2,他引:3
Fanconi anemia (FA) is an autosomal recessive disease marked by developmental defects, bone marrow failure, and cancer susceptibility. FA cells are hypersensitive to DNA cross-linking and alkylating agents and accumulate in the G2 phase of the cell cycle in response to these agents. FA cells also display genomic instability, suggesting a possible defect in the p53 pathway. To test the effect of heterologous expression of FAC cDNA on drug-induced cytotoxicity, G2 accumulation, and p53 induction in FA cells, we compared two isogenic FA cell lines: HSC536N (mock), a FA type C cell line sensitive to mitomycin C (MMC), and the same cell line transfected (corrected) with wild-type FAC cDNA (HSC536N [+FAC]). HSC536N (+FAC) cells showed a 30-fold increase in resistance to MMC concentration. Similarly, increases in resistance were observed following exposure to cisplatin, carboplatin, and cyclophosphamide. In addition, HSC536N (+FAC) cells showed a twofold lower G2 accumulation following MMC treatment. To analyze the possible interaction of FAC with the p53 pathway, we analyzed p53 induction in mock and corrected cell lines following exposure to MMC. HSC536N (mock) cells induced p53 at lower MMC concentrations than HSC536N (corrected). Caffeine, a known G2 checkpoint inhibitor, not only inhibited G2 accumulation seen in both cell lines but also caused the resistant HSC536N (+FAC) to become as sensitive to MMC as HSC536N (mock) cell line. We conclude that the FAC protein has a specific cytoprotective effect and may function as a cell cycle regulator of the G2 phase of the cell cycle. 相似文献
82.
Riccardo Giovannone Gian Maria Busetto Gabriele Antonini Ottavio De Cobelli Matteo Ferro Stefano Tricarico Francesco Del Giudice Giulia Ragonesi Simon L. Conti Giuseppe Lucarelli Vincenzo Gentile Ettore De Berardinis 《Medicine》2015,94(39)
Erectile dysfunction (ED) is inability to achieve and maintain an erection to permit satisfactory sexual activity. Homocysteine (Hcys) is a sulfur-containing amino acid synthesized from the essential amino acid methionine. Experimental models have elucidated the role of hyperhomocysteinemia (HHcys) as a strong and independent predictor for atherosclerosis progression and impaired cavernosal perfusion.The aim of this study is to investigate the serum levels of Hcys in our cohort of patients with ED, to compare these values with these of control population and to examine Hcys as a predictive marker for those patients who are beginning to complain mild–moderate ED.A total of 431 patients were enrolled in the study. The whole cohort was asked to complete the International Index of Erectile Function (IIEF) questionnaire. The study population was divided in 3 main groups: Group A: 145 patients with no ED serving as a control group; Group B: 145 patients with mild or mild–moderate ED; Group C: 141 patients with moderate or severe ED. Each participant underwent blood analysis. All patients underwent baseline and dynamic penile Doppler ultrasonography.We found in our cohort mean Hcys plasma concentrations significantly higher than the cut-off point in both groups B and C (18.6 ± 4.7 and 28.38 ± 7.8, respectively). Mean IIEF score was 27.9 ± 1.39, 19.5 ± 2.6, and 11.1 ± 2.5 for groups A, B, and C, respectively (P < 0.0001). In the penile Doppler ultrasonography studies, a high significant inverse correlation was detected between the mean values of the 10th minute''s peak-systolic velocity (PSV) and Hcys levels for the groups B and C.This establishes a dose-dependent association between Hcys and ED. Furthermore, we showed that Hcys was an earlier predictor of ED than Doppler studies, as the Hcys increase was present in patients with mild ED even before abnormal Doppler values. 相似文献
83.
由于在瓣膜区域、左心室松弛性和僵直性等方面易于发生混淆.传统多普勒测量对二尖瓣疾病病人左心房压的预测上受到限制。然而,在犬和临床研究中,组织多普勒成像所测定的充盈早期二尖瓣血流速率起始段和房室环的充盈早期速率之间的时间窗(time interval between the onset of early diastolic mitral inflow velocity and annular early diastolic velocity,TE-Ea)与左心室舒张时间常数(time constant of left ventricular relaxation,t)良好相关,并且不受上述瓣膜区域、左心室舒张和僵直等变量的影响。因此在病人人群中开展这项研究,检验其用途。 相似文献
84.
The significance of HLA-DRB1 matching on clinical outcome after HLA-A, B, DR identical unrelated donor marrow transplantation 总被引:11,自引:14,他引:11
Petersdorf EW; Longton GM; Anasetti C; Martin PJ; Mickelson EM; Smith AG; Hansen JA 《Blood》1995,86(4):1606-1613
Despite matching for serologically defined HLA-A, B, DR antigens, acute graft-versus-host disease (GVHD) is a major complication contributing to increased morbidity and mortality in patients who undergo marrow transplantation from unrelated donors. The extent to which unrecognized mismatching for alleles that encode DR1-DR18 contribute to the increased risk of acute GVHD and overall survival is unknown. We analyzed 364 patients and their HLA-A, B, DR serologically matched donors to determine whether molecular typing of DRB1 alleles can allow more accurate donor/recipient matching and thereby improve clinical outcome after marrow transplantation. DRB1 alleles were typed by sequence-specific oligonucleotide probe hybridization methods. Selected alleles were confirmed by DNA sequencing. Of the 364 pairs, 305 were matched and 59 were mismatched for DRB1. The probability of moderate to severe acute GVHD was .48 for the matched and .70 for the mismatched patients. Compared with mismatched patients, the estimated relative risk (RR) of GVHD for matched patients was .58 (95% confidence interval [CI], .40 to .85). DRB1 matching decreased the risk of transplant- related mortality (RR, .66; 95% CI, .44 to .97) and was associated with decreased overall mortality (RR, .71; 95% CI, .51 to 1.0). Therefore, matching DRB1 alleles of the donor and recipient decreases the risk of acute GVHD and improves survival after unrelated marrow transplantation. These results indicate that prospective matching of patients and donors for DRB1 alleles is warranted. 相似文献
85.
Schmidt GM; Bross KJ; Blume KG; Enders N; Santos S; Novitski M; Chillar RK 《Blood》1980,55(2):299-303
An immunohistochemical procedure for the detection of immunoglobulin G adherent to platelets is described. The peroxidase anti-peroxidase method is used to detect antibody activity directed against platelets from normal donors in the sera from 305 individuals. These subjects were divided into three groups: group 1, patients referred for tissue typing; group 2, healthy normal females; group 3, healthy normal males. In group 1, 28% of the sera were found to be positive; in most of these a history of prior transfusions was obtained. In group 2, 7.4% were found to be positive, most having previous pregnancies. Only 1% were found to be positive in group 3, and no reason for presensitization was found. Results from the indirect immunofluorescence technique served as a control and as a means to compare the sensitivity. Under the conditions chosen, the peroxidase anti-peroxidase test was two to eight times more sensitive than the immunofluorescence technique. Specificity of the peroxidase anti-peroxidase technique was demonstrated using a monospecific anti-PLA1 antiserum. It is concluded that the peroxidase anti-peroxidase slide technique may be a useful tool in the study of platelet-related immunophenomena. 相似文献
86.
GM Makhlouf 《Gastroenterology》1997,112(6):2111-2113
This article has no abstract. To view the article, select the "View Print Version (PDF)" link above. 相似文献
87.
Sala A; Aliev GM; Rossoni G; Berti F; Buccellati C; Burnstock G; Folco G; Maclouf J 《Blood》1996,87(5):1824-1832
Morphological and functional modifications occurring in Langendorff rabbit heart preparations perfused with purified human leukocytes (PMNL), as an organ model of sulfidopeptide-leukotrienes (sLT) transcellular biosynthesis, were studied. Coronary perfusion pressure (CPP), monitored as an index of coronary vasospasm, increased by 295% after challenge with the Ca(2+)-ionophore A-23187 (0.5 micromol/L) for 30', accompanied by a significant formation of sLT. Increase in CPP was prevented by PMNL pretreatment with the 5-lipoxygenase inhibitor MK-886 (1 micromol/L) or by heart pretreatment with LTD4-receptor antagonist SKF 104353, indicating a pivotal role of PMNL-derived 5-lipoxygenase (5- LO) products in the observed functional modifications. Similar effects were obtained using granulocyte macrophage-colony stimulating factor- primed PMNL challenged with the tripeptide n-formyl-methionyl-leucyl- phenylalanine. Scanning electron microscopy (SEM) of coronary arteries showed craters on the vessel luminal surface, PMNL adhering to endothelial cells (EC), increased number of microvilli on EC, presence of nonviable, desquamating, fusiform EC. SEM and transmission electron microscopy of myocardial microvessels, showed presence of perivascular and intermuscle edema, presence of activated PMNL and decreased number of patent microvessels. These morphological alterations were significantly blunted by MK-886 or SKF 104353. These data provide evidence of close interaction between PMNL and myocardial EC, resulting in enhanced sLT formation via transcellular biosynthesis, originating from transfer of PMNL-derived LTA4 to EC. These potent proinflammatory autacoids are responsible for coronary vasospasm and the morphological alternations observed. 相似文献
88.
Human platelets exert cytotoxic effects on tumor cells 总被引:6,自引:0,他引:6
Monocytes are thought to play a role in host resistance to tumor cell growth in animals and humans. In addition, platelets are known to be involved in tumor metastases. To investigate the interaction of these two cell types and their effect on tumor cells, human monocytes and platelets were examined using an in vitro monocyte-tumor cell cytotoxicity assay. Monocytes alone resulted in 32% +/- 1.5 (mean +/- SEM) tumor cell kill. When platelets were added to monocytes in a 1:1 ratio, an increase in cytotoxicity to 61% +/- 3.2 was observed. The cytotoxicity noted when platelets were added to a fixed number of monocytes and tumor cells was dependent on the number of platelets added. A decrease in cytotoxicity from 32% +/- 1.5 to 12% +/- 2.3 was observed when contaminating platelets were removed from monocyte preparations. Platelets added to tumor cells in the absence of any monocytes were also toxic, resulting in a maximum kill of 95% at a 4:1 platelet/tumor cell ratio. Secreted products of freshly isolated platelets may be responsible for much of the observed cytotoxicity, since supernatants from the platelets were toxic for tumor cells. Platelets pretreated with a cyclooxygenase inhibitor (ASA) or a lipoxygenase inhibitor had decreased cytotoxicity compared with untreated platelets. Our results indicate that products of platelet arachidonate metabolism are toxic for tumor cell lines. They also suggest that the role of the platelet must be considered when studying monocyte-tumor cell cytotoxicity. 相似文献
89.
A comparative analysis of enzymatic activities has been performed on 47 human continuous lymphoid lines: 22 tumors derived from Burkitt's lymphoma lines, 6 other lymphomatous long-term cultures, and 19 nonmalignant ties determined on the cell extracts. 4 showed no significant differences between the various lines. They included adenosine diphosphoribose incorporation, glucose-6-phosphate dehydrogenase, cyclic-AMP phosphodiesterase, and glutathione reductase. However, striking differences of activity were found for the enzyme, NAD(P) glycohydrolase (EC 3.2.2.6). Activity levels were, as a mean, four times higher in Burkitt's lymphoma-derived cell lines than in nonmalignant control lines, and the difference was highly significant (p less than 0.02). All Burkitt cell lines containing translocations of chromosome 8 with either chromosomes 2, 14 or 22 showed an increased activity. The specificity and significance of this possible enzymatic marker of Burkitt's lymphoma cells is discussed. 相似文献
90.
Bone marrow transplantation for patients with Philadelphia chromosome- positive acute lymphoblastic leukemia 总被引:1,自引:2,他引:1
Forman SJ; O'Donnell MR; Nademanee AP; Snyder DS; Bierman PJ; Schmidt GM; Fahey JL; Stein AS; Parker PM; Blume KG 《Blood》1987,70(2):587-588
We report the treatment outcome of allogeneic bone marrow transplantation in ten patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Six patients are alive and well for 6 to 30 months (median 19 months) after transplantation. Four patients died with transplant related complications. In view of the poor prognosis associated with this disease, marrow ablation followed by allogeneic or syngeneic marrow grafting may be the preferred treatment modality if a suitable marrow donor is available. 相似文献