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81.
Concomitant MDS with isolated 5q deletion and MGUS: case report and review of molecular aspects 下载免费PDF全文
Florian Nolte Maximilian Mossner Johann‐Christoph Jann Daniel Nowak Tobias Boch Nadine Zoe Müller Wolf‐Karsten Hofmann Georgia Metzgeroth 《European journal of haematology》2017,98(3):302-310
Patients with monoclonal gammopathy of undetermined significance (MGUS) have a higher risk for the development of concomitant primary cancers such as multiple myeloma (MM) and myelodysplastic syndrome (MDS). We report the case of patient initially suffering from MGUS of the IgG lambda subtype for more than 10 yr, which evolved to MM and MDS with deletion (5q) with severe pancytopenia. Due to pancytopenia, he received dose‐reduced treatment with lenalidomide and dexamethasone. He achieved an ongoing transfusion independency after about 1 month of treatment. Bone marrow taken 14 months after start of treatment showed a complete cytogenetic response of the del(5q) clone and a plasma cell infiltration below 5%. In contrast to the development of MM in MGUS patients, the subsequent occurrence of MDS after diagnosis of MGUS is infrequent. Moreover, the biological association of MDS with MGUS is not sufficiently understood, but the non‐treatment‐related occurrence supports the pathogenetic role of pre‐existing alterations of stem cells. Here, we summarize data on concomitant MDS and MGUS/MM with particular emphasis on molecular aspects. 相似文献
82.
Stefan Stefanovic Florian Schuetz Christof Sohn Philipp Beckhove Christoph Domschke 《Cancer metastasis reviews》2014,33(1):309-320
Breast cancer is a systemic disease with a primarily local component. Besides surgical resection and irradiation of the locoregional tumor setting, central therapeutic aim is the elimination of disseminated micrometastatic tumor cells using cytostatic and/or hormonal treatment. Nevertheless, in the course of time a majority of patients suffer from systemic recurrence in the form of distant metastases. Intriguingly, in this connection, intratumoral cytotoxic T lymphocytes might serve as independent predictors of treatment efficacy and clinical outcome. Loss of immune balance (tumor dormancy) during intensive cross talk between T cells and tumor cells in the bone marrow microenvironment is suggested one reason for distant metastatic relapse. In this clinical context, further supportive therapies become increasingly attractive, taking immunological features of breast cancer cells into special account. The present review aims to dissect bone marrow-derived cellular antitumor immune responses and translational immunologic treatment options regarding their actual relevance to patients’ clinical benefit and their future directions in breast cancer management. 相似文献
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Laurent Gueudré Tomas Binder Christian Chmelik Florian Hibbe Douglas M. Ruthven J?rg K?rger 《Materials》2012,5(4):721-740
Because of the small particle size, orientation-dependent diffusion measurements in microporous materials remains a challenging task. We highlight here the potential of micro-imaging by interference microscopy in a case study with MFI-type crystals in which, although with different accuracies, transient concentration profiles in all three directions can be observed. The measurements, which were performed with “rounded-boat” shaped crystals, reproduce the evolution patterns of the guest profiles recorded in previous studies with the more common “coffin-shaped” MFI crystals. The uptake and release patterns through the four principal faces (which in the coffin-shaped crystals extend in the longitudinal direction) are essentially coincident and there is no perceptible mass transfer in the direction of the long axis. The surface resistances of the four crystal faces through which mass transfer occurs are relatively small and have only a minor effect on the mass transfer rate. As a result of the pore structure, diffusion in the crystallographic c direction (which corresponds to the direction of the long axis) is expected to be much slower than in the transverse directions. This could explain the very low rate of mass transfer observed in the direction of the long axis, but it is also possible that the small end faces of the crystal may have high surface resistance. It is not possible to distinguish unequivocally between these two possibilities. All guest molecules studied (methyl-butane, benzene and 4-methyl-2-pentyne) show the same orientation dependence of mass transfer. The long 4-methyl-2-pentyne molecules would be expected to propagate at very different rates through the straight and sinusoidal channels. The coinciding patterns for uptake through the mutually perpendicular crystal faces therefore provide clear evidence that both the coffin shaped crystals and the rounded-boat-shaped crystals considered in this study, must be intergrowths rather than pure single crystals. 相似文献
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Henry J. Esber PhD Florian F. Menninger Jr. PhD Arthur E. Bogden PhD Marcus M. Mason DVM 《Archives of environmental & occupational health》2013,68(2):99-104
Inhalation of cigarette whole smoke (CWS) or its vapor phase (CVP) significantly impaired immune response capability in mice. Significant immunosuppressive effects on the humoral antibody response to a single antigenic stimulus were evident in animals exposed to smoke for seven days before or two days after administration of antigen. Impairment of the immunological response capability appeared to be temporary, with recovery about 14 days after exposure. Different lengths of exposure prior to antigenic stimulation neither produced an additive impairment of the immunological response nor rendered the experimental animals more tolerant to CWS or CVP. The immunological deficiency was specific to CWS and CVP inhalation rather than to nonspecific debilitating stress factors. The inductive phase was the period of the primary and secondary immune response most sensitive to impairment by exposure to CWS or CVP. 相似文献
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Economic evaluation of chronic lymphocytic leukemia from a hospital management perspective 下载免费PDF全文
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The GTPase K-ras is involved in a variety of cellular processes such as differentiation, proliferation and survival. However, activating mutations, which frequently occur in many types of cancer, turn KRAS into one of the most prominent oncogenes. Likewise, miR-200c is a key player in tumorigenesis functioning as a molecular switch between an epithelial, non-migratory, chemosensitive and a mesenchymal, migratory, chemoresistant state. While it has been reported that KRAS is modulated by several tumor suppressor miRNAs, this is the first report on the regulation of KRAS by miR-200c, both playing a pivotal role in oncogenesis. We show that KRAS is a predicted target of miR-200c and that the protein expression of KRAS inversely correlates with the miR-200c expression in a panel of human breast cancer cell lines. KRAS was experimentally validated as a target of miR-200c by Western blot analyses and luciferase reporter assays. Furthermore, the inhibitory rffect of miR-200c-dependent KRAS silencing on proliferation and cell cycle was demonstrated in dfferent breast and lung cancer cell lines. Thereby, the particular role of KRAS was dissected from the role of all the other miR-200c targets by specific knockdown experiments using siRNA against KRAS. Cell lines harboring an activating KRAS mutation were similarly affected by miR-200c as well as by the siRNA against KRAS. However, in a cell line with wild-type KRAS only miR-200c was able to change proliferation and cell cycle. Our findings suggest that miR-200c is a potent inhibitor of tumor progression and therapy resistance, by regulating a multitude of oncogenic pathways including the RAS pathway. Thus, miR-200c may cause stronger anti-tumor efffects than a specific siRNA against KRAS, emphasizing the potential role of miR-200c as tumor suppressive miRNA 相似文献