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61.
62.
Sara Meril Ortal Harush Yishai Reboh Tatyana Matikhina Tilda Barliya Cyrille J. Cohen 《Molecular carcinogenesis》2020,59(7):713-723
Chimeric antigen receptor (CAR) T-cells treatment demonstrate the increasing and powerful potential of immunotherapeutic strategies, as seen mainly for hematological malignancies. Still, efficient CAR-T cell approaches for the treatment of a broader spectrum of tumors are needed. It has been shown that cancer cells can implement strategies to evade immune response that include the expression of inhibitory ligands, such as hypersialylated proteins (sialoglycans) on their surface. These may be recognized by sialic acid-binding immunoglobulin-type lectins (siglecs) which are surface receptors found primarily on immune cells. In this regard, siglec-7 and -9 are found on immune cells, such as natural killer cells, T-cells, and dendritic cells and they can promote immune suppression when binding to sialic acids expressed on target cells. In the present study, we hypothesized that it is possible to use genetically engineered T-cells expressing siglec-based CARs, enabling them to recognize and eliminate tumor cells, in a non-histocompatibility complex molecule restricted way. Thus, we genetically modified human T-cells with different chimeric receptors based on the exodomain of human siglec-7 and -9 molecules and selected optimal receptors. We then assessed their antitumor activity in vitro demonstrating the recognition of cell lines from different histologies. These results were confirmed in a tumor xenograft model exemplifying the potential of the present approach. Overall, this study demonstrates the benefit of targeting cancer-associated glycosylation patterns using CAR based on native immune receptors and expressed in human primary T-cells. 相似文献
63.
Hiroki Katagiri Luis Filipe Mendes Frank P. Luyten 《Journal of tissue engineering and regenerative medicine》2019,13(5):846-856
Nude mice have been extensively used to investigate the potency of tissue engineering strategies for bone repair. However, the contribution of pro‐inflammatory and proregenerative stimuli of the host for the process of new bone formation and integration remains poorly understood. In this study, ectopic bone formation was investigated in nude (Nu) versus wild‐type (WT) mice. Calcium phosphate (CaP) scaffolds (CopiOs [Zimmer] and Bio‐Oss [Geistlich]) were loaded with different concentrations of rhBMP6 (40, 120, and 240 ng/mm3 rhBMP6) and implanted subcutaneously in Nu (BALB/c and NMR1) and WT (BALB/c and c57BL/6) mice. CaP scaffolds loaded with rhBMP6 did not form bone in WT mice. However, in Nu mice, 40 ng/mm3 rhBMP6 was sufficient to generate relevant volumes of new bone at 6 weeks after implantation. Looking into potential underlying mechanisms, TNF‐α blocking antibodies were injected intraperitoneally but could not restore bone formation. Also, mouse periosteal cells (mPDCs) seeded in CopiOs loaded with rhBMP6 did not significantly improve the outcome. Abrogation of bone formation was associated with dense cellular infiltration, in particular with the presence of CD3+ T‐lymphocytes. To probe a correlation between calcium ions and impaired bone formation in WT mice, type 1 collagen gels were loaded with rhBMP6 and calcium chloride and injected subcutaneously. These gels generated new bone in WT mice despite the increased percentage of CD3+ cells at Day 3 after implantation as compared with control gels. Overall, this study illustrated the negative effect of the inflammatory host response on the bone‐forming capacity of rhBMP6 coated on bioceramic scaffolds. 相似文献
64.
Fauzi Mh Busra Nor Fadilah Rajab Yasuhiko Tabata Aminuddin B. Saim Ruszymah B.H. Idrus Shiplu R. Chowdhury 《Journal of tissue engineering and regenerative medicine》2019,13(5):874-891
The full‐thickness skin wound is a common skin complication affecting millions of people worldwide. Delayed treatment of this condition causes the loss of skin function and integrity that could lead to the development of chronic wounds or even death. This study was aimed to develop a rapid wound treatment modality using ovine tendon collagen type I (OTC‐I) bio‐scaffold with or without noncultured skin cells. Genipin (GNP) and carbodiimide (EDC) were used to cross‐link OTC‐I scaffold to improve the mechanical strength of the bio‐scaffold. The physicochemical, biomechanical, biodegradation, biocompatibility, and immunogenicity properties of OTC‐I scaffolds were investigated. The efficacy of this treatment approach was evaluated in an in vivo skin wound model. The results demonstrated that GNP cross‐linked OTC‐I scaffold (OTC‐I_GNP) had better physicochemical and mechanical properties compared with EDC cross‐linked OTC‐I scaffold (OTC‐I_EDC) and noncross‐link OTC‐I scaffold (OTC‐I_NC). OTC‐I_GNP and OTC‐I_NC demonstrated no toxic effect on cells as it promoted higher cell attachment and proliferation of both primary human epidermal keratinocytes and human dermal fibroblasts compared with OTC‐I_EDC. Both OTC‐I_GNP and OTC‐I_NC exhibited spontaneous formation of bilayer structure in vitro. Immunogenic evaluation of OTC‐I scaffolds, in vitro and in vivo, revealed no sign of immune response. Finally, implantation of OTC‐I_NC and OTC‐I_GNP scaffolds with noncultured skin cells demonstrated enhanced healing with superior skin maturity and microstructure features, resembling native skin in contrast to other treatment (without noncultured skin cells) and control group. The findings of this study, therefore, suggested that both OTC‐I scaffolds with noncultured skin cells could be promising for the rapid treatment of full‐thickness skin wound. 相似文献
65.
Christine Mlzer Sucharita P. Shankar Vlad Masalski May Griffith Lucia Kuffov John V. Forrester 《Journal of tissue engineering and regenerative medicine》2019,13(9):1507-1517
We showed previously that 1‐ethyl‐3‐(3‐dimethylamino‐propyl)‐carbodiimide hydrochloride (EDC) cross‐linked recombinant human collagen III hydrogels promoted stable regeneration of the human cornea (continued nerve and stromal cell repopulation) for over 4 years. However, as EDC cross linking kinetics were difficult to control, we additionally tested a sterically bulky carbodiimide. Here, we compared the effects of two carbodiimide cross linkers—bulky, aromatic N‐cyclohexyl‐N0‐(2‐morpholinoethyl)‐carbodiimide (CMC), and nonbulky EDC—in a mouse corneal graft model. Murine corneas undergoing full‐thickness implantation with these gels became opaque due to dense retro‐corneal membranes (RCM). Corneal epithelial cytokeratin 12 and alpha smooth muscle actin indicative of functional tissue regeneration and wound contraction were observed in RCM surrounding both hydrogel types. However, quantitatively different levels of infiltrating CD11c+ dendritic cells (DC) were found, suggesting a hydrogel‐specific innate immune response. More DC infiltrated the stroma surrounding EDC‐N‐hydroxysuccinimide (NHS) hydrogels concurrently with higher fibrosis‐associated tenascin c expression. The opposite was true for CMC‐NHS gels that had previously been shown to be more tolerising to DC. In vitro studies showed that DC cultured with transforming growth factor β1 (TGF‐β1) induced fibroblasts to secrete more tenascin c than those cultured with lipopolysaccharide and this effect was blocked by TGF‐β1 neutralisation. Furthermore, tenascin c staining was found in 40‐ to 50μm long membrane nanotubes formed in fibroblast/DC cocultures. We suggest that TGF‐β1 alternatively activated (tolerising) DC regulate fibroblast‐mediated tenascin c secretion, possibly via local production of TGF‐β1 in early wound contraction, and that this is indirectly modulated by different hydrogel chemistries. 相似文献
66.
67.
《Clinical oncology (Royal College of Radiologists (Great Britain))》2020,32(5):303-315
The lung is the preferred site of metastasis from soft tissue sarcoma (STS). This systematic review aims to evaluate the outcomes of stereotactic body radiotherapy (SBRT) and metastasectomy (MTS) for the treatment of lung metastases from STS. A systematic review was carried out according to the PRISMA protocol. PubMed, Medline, EMBASE, Cochrane Library, Ovid and Web of Knowledge databases were searched for English-language articles to December 2018 using a predefined strategy. Retrieved studies were independently screened and rated for relevance. Data were extracted by two researchers. In total, there were 1306 patients with STS: 1104 underwent MTS and 202 had SBRT. The mean age ranged from 40 to 55.8 years in the MTS group and from 47.9 to 64 years in the SBRT group. The cumulative death rate was 72% (95% confidence interval 59–85%) in the MTS group and 56% (38–74%) in the SBRT group. The cumulative mean overall survival time was 46.7 months (36.4–57.0%) in the MTS group and 47.6 months (33.7–61.5%) in the SBRT group. The cumulative rate of patients alive with disease was 5% (2–9%) in the MTS group and 15% (6–36%) in the SBRT group. Finally, the cumulative rate of patients alive without disease in the two groups was 19% (9–29%) and 20% (10–50%), respectively. Our study showed that local treatment of pulmonary metastases from STS with SBRT, compared with surgery, was associated with a lower cumulative overall death rate and similar overall survival time and survival rates without disease. By contrast, SBRT was associated with a higher survival rate with disease than MTS. Large randomised trials are necessary to confirm these findings and to establish whether SBRT may be a reliable option for early stage disease. 相似文献
68.
Soft tissue sarcomas (STS) are rare tumours presenting as soft tissue lumps. Ultrasound is often the primary modality for the initial assessment, with MRI the mainstay for lesion characterisation. PET/CT along with other emerging MRI sequences are used in certain situations as an adjunct and problem solving tool in STS staging and assessment of disease recurrence. Recent advances include the promise of whole body MRI, hybrid PET/MRI, diffusion weighted imaging, dynamic contrast enhanced MRI and advances in artificial intelligence. This article discusses current concepts in extremity STS imaging and highlights recent advances. 相似文献
69.
70.
《Surgery (Oxford)》2021,39(10):648-653
Shock is the clinical syndrome that arises from inadequate cellular oxygen metabolism which can occur when there is either insufficient oxygen delivery or impaired oxygen utilization. As a clinical syndrome, shock is associated with significant morbidity and mortality particularly if there is a delay in recognition or initiation of treatment. There are multiple mechanisms that can result in a shocked state; often clinical examination is insufficient to differentiate between such mechanisms. Clinicians must instead rely on haemodynamic monitoring devices for both diagnosis and the targeting of therapies. In this article we review the basic principles of haemodynamics, the different aetiologies of shock and explore the various haemodynamic monitoring devices available to clinicians. 相似文献