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Manoj G. Damale Rajesh B. Patil Siddique Akber Ansari Hamad M. Alkahtani Abdulrahman A. Almehizia Devanand B. Shinde Rohidas Arote Jaiprakash Sangshetti 《RSC advances》2019,9(45):26176
The enzyme pantothenate synthetase panC is one of the potential new antimicrobial drug targets, but it is poorly characterized in H. pylori. H. pylori infection can cause gastric cancer and the management of H. pylori infection is crucial in various gastric ulcers and gastric cancer. The current study describes the use of innovative drug discovery and design approaches like comparative metabolic pathway analysis (Metacyc), exploration of database of essential genes (DEG), homology modelling, pharmacophore based virtual screening, ADMET studies and molecular dynamics simulations in identifying potential lead compounds for the H. pylori specific panC. The top ranked virtual hits STOCK1N-60270, STOCK1N-63040, STOCK1N-44424 and STOCK1N-63231 can act as templates for synthesis of new H. pylori inhibitors and they hold a promise in the management of gastric cancers caused by H. pylori.Computational approaches such as pharmacophore modeling, virtual screening and MD simulations were explored to find the potential hits as H. pylori specific panC inhibitors for the management of gastric ulcers and gastric cancers. 相似文献
83.
Anwer Md. Khalid Mohammad Muqtader Iqbal Muzaffar Ansari Mohd Nazam Ezzeldin Essam Fatima Farhat Alshahrani Saad M. Aldawsari Mohammed F. Alalaiwe Ahmed Alzahrani Aiman A. Aldayel Abdullah M. 《Journal of thrombosis and thrombolysis》2020,49(3):404-412
Journal of Thrombosis and Thrombolysis - The purpose of the currents study was to enhance bioavailability of rivaroxaban (RXB) and reduce the food effect. RXB loaded PLGA nanoparticles... 相似文献
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Gabriel Duette Bonnie Hiener Hannah Morgan Fernando G. Mazur Vennila Mathivanan Bethany A. Horsburgh Katie Fisher Orion Tong Eunok Lee Haelee Ahn Ansari Shaik Rmi Fromentin Rebecca Hoh Charline Bacchus-Souffan Najla Nasr Anthony L. Cunningham Peter W. Hunt Nicolas Chomont Stuart G. Turville Steven G. Deeks Anthony D. Kelleher Timothy E. Schlub Sarah Palmer 《The Journal of clinical investigation》2022,132(7)
Despite long-term antiretroviral therapy (ART), HIV-1 persists within a reservoir of CD4+ T cells that contribute to viral rebound if treatment is interrupted. Identifying the cellular populations that contribute to the HIV-1 reservoir and understanding the mechanisms of viral persistence are necessary to achieve an effective cure. In this regard, through Full-Length Individual Proviral Sequencing, we observed that the HIV-1 proviral landscape was different and changed with time on ART across naive and memory CD4+ T cell subsets isolated from 24 participants. We found that the proportion of genetically intact HIV-1 proviruses was higher and persisted over time in effector memory CD4+ T cells when compared with naive, central, and transitional memory CD4+ T cells. Interestingly, we found that escape mutations remained stable over time within effector memory T cells during therapy. Finally, we provided evidence that Nef plays a role in the persistence of genetically intact HIV-1. These findings posit effector memory T cells as a key component of the HIV-1 reservoir and suggest Nef as an attractive therapeutic target. 相似文献
87.
With the development and widespread use of flexible endoscopes, injection sclerotherapy of oesophageal varices has advanced beyond the early stages. Although slightly different techniques and different sclerosants are used, the results are not strikingly different. The cumulative rate of adverse effects is in the range of 20 to 40%, with a procedure-related mortality of around 1 to 2%. Sclerotherapy is the best available treatment for haemostasis of acute oesophageal variceal bleeding. However, as a long-term therapy it is less effective in the prevention of recurrent gastrointestinal bleeding events, since obliteration of all varices often takes several months. Furthermore, extra-oesophageal bleeding is not amenable to sclerotherapy. Thus, if repeated injections fail to prevent recurrent bleeding, other options such as shunt surgery, transection, chronic medical portal decompression with beta-blockers or even liver transplantation should be considered according to the needs of the individual patient. Prophylaxis of first variceal haemorrhage was beneficial in selected patients with a high bleeding risk. It cannot, however, be generally recommended at present. 相似文献
88.
Saif Akhter Ansari James Andrew Kennedy Fizan Younis 《Journal of hand and microsurgery》2022,14(1):71
Introduction Early review of skin graft following dermofasciectomy with skin grafting for Dupuytren’s disease is not standard practice because of the potentially adverse effects on inosculation and neovascularization process of the skin grafting. The purpose of this retrospective case series was to observe whether early review of grafts postoperatively at 48 hours adversely affects graft survival and surgical outcomes. Materials and Methods Forty-nine primary and revision procedures were retrospectively analyzed for treatment outcomes, postoperative complications, functional hand scoring, and satisfaction rates postoperatively. Results Thirty-eight patients were treated successfully with no postoperative contracture. There were three treatment failures and two graft failures, with two amputations within these failures. Paired pre- and postoperative Unité Rhumatologique des Affections de la Main scoring demonstrated significant improvement in hand function for primary procedures, with a mean satisfaction score of 7.7 out of 10. Conclusion We have shown early graft review following dermofasciectomy and full-thickness skin grafting to be safe, allowing early mobilization and splinting, with our postoperative failure and complication rate being within published literature. 相似文献
89.
Uma Bhandari M. Nazam Ansari F. Islam C.D. Tripathi 《Indian journal of pharmacology》2008,40(4):152-157
Objective:
The present study was designed to evaluate the effect of the aqueous extract of Embelia ribes Burm fruits on methionine-induced hyperhomocysteinemia, hyperlipidemia and oxidative stress in albino rats.Materials and Methods:
Adult male Wistar albino rats were fed with the aqueous extract of Embelia ribes (100 and 200 mg/kg, p.o.) for 30 days. Hyperhomocysteinemia was induced by methionine treatment (1 g/kg, p.o.) for 30 days and folic acid (100 mg/kg, p.o.) was used as a standard drug. The animals were evaluated for various biochemical parameters in serum and brain homogenates, followed by histopathological studies at the end of the study.Results:
Administration of methionine (1 g/kg, p.o.) for 30 days to vehicle control rats produced significant increase (P < 0.01) in homocysteine, lactate dehydrogenase (LDH), total cholesterol, triglycerides, low density lipoprotein (LDL-C), very low density lipoprotein (VLDL-C) levels in serum and lipid peroxides (LPO) levels in brain homogenates, with reduction in high density lipoprotein (HDL-C) levels in serum, and glutathione (GSH) content in brain homogenates, as compared to vehicle control rats. Administration of the aqueous extract of Embelia ribes (100 and 200 mg/kg, p.o.) for 30 days, to hyperhomocysteinemic rats, significantly (P < 0.01) decreased the levels of homocysteine, LDH, total cholesterol, triglycerides, LDL-C and VLDL-C and increased the HDL-C levels in serum. In addition, a significant (P < 0.01) decrease in LPO levels with increase in GSH content was observed in hyperhomocysteinemic rats treated with the aqueous extract of Embelia ribes. The results were comparable to those obtained with folic acid, a standard antihyperhomocysteinemic drug.Conclusion:
The present results provide clear evidence that the aqueous extract of Embelia ribes treatment enhances the antioxidant defense against methionine-induced hyperhomocysteinemia, hyperlipidemia and oxidative stress in brain. 相似文献90.
Jonathan M. Fishman Mark W. Lowdell Luca Urbani Tahera Ansari Alan J. Burns Mark Turmaine Janet North Paul Sibbons Alexander M. Seifalian Kathryn J. Wood Martin A. Birchall Paolo De Coppi 《Proceedings of the National Academy of Sciences of the United States of America》2013,110(35):14360-14365
Decellularized (acellular) scaffolds, composed of natural extracellular matrix, form the basis of an emerging generation of tissue-engineered organ and tissue replacements capable of transforming healthcare. Prime requirements for allogeneic, or xenogeneic, decellularized scaffolds are biocompatibility and absence of rejection. The humoral immune response to decellularized scaffolds has been well documented, but there is a lack of data on the cell-mediated immune response toward them in vitro and in vivo. Skeletal muscle scaffolds were decellularized, characterized in vitro, and xenotransplanted. The cellular immune response toward scaffolds was evaluated by immunohistochemistry and quantified stereologically. T-cell proliferation and cytokines, as assessed by flow cytometry using carboxy-fluorescein diacetate succinimidyl ester dye and cytometric bead array, formed an in vitro surrogate marker and correlate of the in vivo host immune response toward the scaffold. Decellularized scaffolds were free of major histocompatibility complex class I and II antigens and were found to exert anti-inflammatory and immunosuppressive effects, as evidenced by delayed biodegradation time in vivo; reduced sensitized T-cell proliferative activity in vitro; reduced IL-2, IFN-γ, and raised IL-10 levels in cell-culture supernatants; polarization of the macrophage response in vivo toward an M2 phenotype; and improved survival of donor-derived xenogeneic cells at 2 and 4 wk in vivo. Decellularized scaffolds polarize host responses away from a classical TH1-proinflammatory profile and appear to down-regulate T-cell xeno responses and TH1 effector function by inducing a state of peripheral T-cell hyporesponsiveness. These results have substantial implications for the future clinical application of tissue-engineered therapies.Although replacement of airways (1–6) or urogenital tissue (7) using stem cell-based techniques has been achieved, engineering of functional contractile muscle tissue has only been partially explored (8–9). While debates have been generated around which myogenic progenitors (satellite cells, muscle stem cells, or myoblasts) should be used, fewer studies have focused on exploring which matrix could offer a better platform for regeneration (10, 11).Autologous tissue-engineered solutions have the major advantage of not requiring immunosuppression, but clinical applications are limited to static organs and tissues, such as skin, or those that can function through passive movement alone, such as trachea, heart valves, blood vessels, and bladder (4, 7, 12). The field continues to expand and tissue bioengineering has provided, or is close to delivering, functional human organ replacements elsewhere (6, 7, 13–17). The ability to produce innervated and revascularized muscles would hugely extend the possible applications of regenerative medicine (18–26).Decellularized skeletal muscle has been characterized by several groups, but its effect on cell-mediated immunity has not been studied (27–30). Here, we provide evidence that decellularized muscle scaffolds promote anti-inflammatory and immunosuppressive responses both in vitro and in vivo, down-regulate T-cell xeno responses and TH1 effector cytokines in vitro, and polarize the macrophage response in vivo toward an M2 phenotype (i.e., promote alternative pathway activation of macrophages). 相似文献