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Extended long-term culture reveals a highly quiescent and primitive human hematopoietic progenitor population 总被引:5,自引:17,他引:5
Long-term culture-initiating cells (LTC-IC) are hematopoietic progenitors able to generate colony-forming unit-cells (CFU) after 5 to 8 weeks (35 to 60 days) of culture on bone marrow (BM) stroma and represent the most primitive progenitors currently detectable in vitro. We have recently reported that long-term cultures initiated with CD34+CD38- cells from BM or cord blood are able to continue generating CFU for at least 100 days, ie, beyond the standard LTC-IC period. In this report, single-cell cultures from cord blood and retroviral marking of cord blood and BM were used to study whether the subpopulation of CD34+CD38- cells able to generate CFU beyond 60 days ("extended long-term culture-initiating cells" or ELTC-IC) are functionally distinct from LTC-IC in terms of timing of initial clonal proliferation and generative capacity. All cord blood LTC-IC formed clones of greater than 50 cells by day 30. In contrast, cord blood ELTC- IC proliferated later in culture, 50% forming clones after day 30. Although efficient retroviral marking of LTC-IC was seen (25% to 45%), marking of ELTC-IC was inefficient (< 1%), consistent with a more quiescent progenitor population. There was a positive correlation between time of clonal proliferation and generative capacity. ELTC-IC generated threefold to fourfold more progeny than did LTC-IC (P < .002). These studies show that there is a functional hierarchy of progenitors in long-term culture which correlates with their level of quiescence. By extending the LTC-IC assay, a more primitive progenitor may be studied that may be functionally closer to the human long-term repopulation stem cell in vivo. 相似文献
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Susanne J van Veluw Jaco JM Zwanenburg Annemieke JM Rozemuller Peter R Luijten Wim GM Spliet Geert Jan Biessels 《Journal of cerebral blood flow and metabolism》2015,35(4):676-683
Cerebral microinfarcts (CMIs) are common neuropathologic findings in aging and dementia. We explored the spectrum of cortical CMIs that can be visualized with 7T magnetic resonance imaging (MRI). Thirty-three coronal brain slices of 11 individuals with neuropathologically confirmed dementia were subjected to a high-resolution postmortem 7T MRI protocol. First, we identified all visible small (⩽5 mm) intracortical and juxtacortical lesions on postmortem MRI. Lesions were classified as CMI or nonCMI based on histology, and their MR features were recorded. Thirty lesions were identified on the initial MRI evaluation, of which twenty-three could be matched with histology. Histopathology classified 12 lesions as CMIs, all of which were located intracortically. On the basis of their MR features, they could be classified as chronic gliotic CMIs—with or without cavitation or hemorrhagic components—and acute CMIs. Eleven MRI identified lesions were not of ischemic nature and most commonly enlarged or atypically shaped perivascular spaces. Their MRI features were similar to gliotic CMIs with or without cavitation, but these ‘CMI mimics'' were always located juxtacortically. 7T postmortem MRI distinguishes different histopathologic types of cortical CMIs, with distinctive MR characteristics. On the basis of our findings, we propose in vivo rating criteria for the detection of intracortical CMIs. 相似文献
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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
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D.?C.?StefanEmail author N.?Masalu L.?Ngendahayo D.?Amadori M.?Botteghi M.?Mendy N.?A.?Othieno-Aabinya T.?Ngoma F.?Asirwa O.?Balogun W.?Ngwa E.?Vuhahula A?Adesina 《Infectious agents and cancer》2015,10(1):48
According to the World Health Organisation (WHO), deaths from non-communicable diseases (NCDs) will increase globally, with the largest increase being on the African continent. On our continent, projections have indicated that deaths from NCDs will exceed all combined communicable, maternal, perinatal and nutritional diseases as the most common causes of death by 2030. Hence, the importance of a functional and improved pathology system in the diagnosis of cancer cannot be debated.Recently, the African Organization for Research and Training in Cancer (AORTIC) organised its East African regional meeting in Mwanza, Tanzania on 25–26 June 2015, with the focus being ‘Pathology and oncology: Education and training for the future in cancer research’. The main themes of the workshop were around improving cancer care and the role of twinning in Eastern Africa, in particular the Mwanza cancer project, telepathology, e-health and biobanking. The outcomes of a 2 day strategic meeting were developing an efficient and effective plan to guide the improvement in pathology training and cancer research in Africa. 相似文献
70.
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