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71.
Benjamin Coiffard Philipp M. Lepper Eloi Prud’Homme Florence Daviet Nadim Cassir Heinrike Wilkens Sami Hraiech Frank Langer Pascal A. Thomas Martine Reynaud-Gaubert Robert Bals Hans-Joachim Schäfers Laurent Papazian Frederik Seiler 《American journal of transplantation》2021,21(4):1586-1596
It is unknown if solid organ transplant recipients are at higher risk for severe COVID-19. The management of a lung transplantation (LTx) program and the therapeutic strategies to adapt the immunosuppressive regimen and antiviral measures is a major issue in the COVID-19 era, but little is known about worldwide practice. We sent out to 180 LTx centers worldwide in June 2020 a survey with 63 questions, both regarding the management of a LTx program in the COVID-19 era and the therapeutic strategies to treat COVID-19 LTx recipients. We received a total of 78 responses from 15 countries. Among participants, 81% declared a reduction of the activity and 47% restricted LTx for urgent cases only. Sixteen centers observed deaths on waiting listed patients and eight centers performed LTx for COVID-19 disease. In 62% of the centers, COVID-19 was diagnosed in LTx recipients, most of them not severe cases. The most common immunosuppressive management included a decreased dose or pausing of the cell cycle inhibitors. Remdesivir, hydroxychloroquine, and azithromycin were the most proposed antiviral strategies. Most of the centers have been affected by the COVID-19 pandemic and proposed an active therapeutic strategy to treat LTx recipients with COVID-19. 相似文献
72.
Hanno Niess Nikolaus Börner Maximilian Muenchhoff Elham Khatamzas Manfred Stangl Alex Graf Philipp Girl Enrico Georgi Dionysios Koliogiannis Gerald Denk Michael Irlbeck Jens Werner Markus Guba 《American journal of transplantation》2021,21(4):1629-1632
To date, little is known about the duration and effectiveness of immunity as well as possible adverse late effects after an infection with SARS-CoV-2. Thus it is unclear, when and if liver transplantation can be safely offered to patients who suffered from COVID-19. Here, we report on a successful liver transplantation shortly after convalescence from COVID-19 with subsequent partial seroreversion as well as recurrence and prolonged shedding of viral RNA. 相似文献
73.
Jignesh K. Patel Guillaume Coutance Alexandre Loupy Deanna Dilibero Michele Hamilton Michelle Kittleson Evan Kransdorf Babak Azarbal Osamu Seguchi Xiaohai Zhang David Chang Dael Geft Lawrence Czer Shaida Varnous Jon A. Kobashigawa 《American journal of transplantation》2021,21(7):2479-2488
Allosensitization represents a major barrier to heart transplantation (HTx). We assessed the efficacy and safety of complement inhibition at transplant in highly sensitized heart transplant recipients. We performed a single-center, single-arm, open-label trial (NCT02013037). Patients with panel reactive antibodies (PRA) ≥70% and pre–formed donor-specific antibodies (DSA) were eligible. In addition to standard of care, patients received nine infusions of eculizumab during the first 2 months posttransplant. The primary composite endpoint was antibody-mediated rejection (AMR) ≥pAMR2 and/or left ventricular dysfunction during the first year. Secondary endpoints included hemodynamic compromise, allograft rejection, and patient survival. Twenty patients were included. Median cPRA and mean fluorescence intensity of immunodominant DSA were 95% (90%–97%) and 6250 (5000–10 000), respectively. Retrospective B cell and T cell flow crossmatches were positive in 14 and 11 patients, respectively. The primary endpoint occurred in four patients (20%). Survival at 1 year was 90% with no deaths resulting from AMR. In a prespecified analysis comparing treated patients to matched control patients, we observed a dramatic reduction in the risk of biopsy-proven AMR in patients treated with eculizumab (HR = 0.36, 95% CI = 0.14–0.95, p = .032). Our findings support the prophylactic use of complement inhibition for heart transplantation at high immunological risk. ClinincalTrials.gov, NCT02013037. 相似文献
74.
Nathalie Chavarot Gillian Divard Anne Scemla Lucile Amrouche Olivier Aubert Marianne Leruez-Ville Marc O. Timsit Claire Tinel Julien Zuber Christophe Legendre Dany Anglicheau Rebecca Sberro-Soussan 《American journal of transplantation》2021,21(7):2448-2458
Belatacept may increase cytomegalovirus (CMV) disease risk after conversion from CNI-based therapy. We analyzed CMV disease characteristics after belatacept conversion. Propensity score matching was used to compare CMV disease incidence in belatacept- and CNI-treated kidney transplant recipients (KTRs). CMV disease characteristics and risk factors under belatacept were analyzed. In total, 223 KTRs (median age [IQR] 59.2 years [45.4–68.5]) were converted to belatacept (median of 11.5 months [2.5–37.0] post-transplantation); 40/223 (17.9%) developed CMV disease. Independent risk factors included increased age (p = .0164), D+/R− CMV serostatus (p = .0220), and low eGFR at conversion (p = .0355). Among 181 belatacept-treated patients matched to 181 controls, 32/181 (17.7%) experienced CMV disease (vs. 5/181 controls [2.8%]). CMV disease cumulative incidences were 6.33 and 0.91/100 person-years (p-y) in belatacept and control groups, respectively. CMV disease risk was particularly high in elderly patients (converted >70 years) and those with eGFR <30 ml/min; cumulative incidences were 18.4 and 5.2/100 p-y, respectively. CMV diseases under belatacept were atypical, with late-onset disease (24/40 patients [60%]), high CMV seropositivity (27/40, 67%), increased severe and tissue-invasive disease rates (gastrointestinal involvement in 32/40 [80%]) and life-threatening diseases (4/40 [10%]). These findings should stimulate further research to secure the use of belatacept as a valuable rescue therapy in KTRs. 相似文献
75.
Aránzazu Caballero-Marcos Magdalena Salcedo Roberto Alonso-Fernández Manuel Rodríguez-Perálvarez María Olmedo Javier Graus Morales Valentín Cuervas-Mons Alba Cachero Carmelo Loinaz-Segurola Mercedes Iñarrairaegui Lluís Castells Sonia Pascual Carmen Vinaixa-Aunés Rocío González-Grande Alejandra Otero Santiago Tomé Javier Tejedor-Tejada José María Álamo-Martínez Luisa González-Diéguez Flor Nogueras-Lopez Gerardo Blanco-Fernández Gema Muñoz-Bartolo Francisco Javier Bustamante Emilio Fábrega Mario Romero-Cristóbal Rosa Martin-Mateos Julia Del Rio-Izquierdo Ana Arias-Milla Laura Calatayud Alberto A. Marcacuzco-Quinto Víctor Fernández-Alonso Concepción Gómez-Gavara Jordi Colmenero Patricia Muñoz José A. Pons the Spanish Society of Liver Transplantation 《American journal of transplantation》2021,21(8):2876-2884
The protective capacity and duration of humoral immunity after SARS-CoV-2 infection are not yet understood in solid organ transplant recipients. A prospective multicenter study was performed to evaluate the persistence of anti-nucleocapsid IgG antibodies in liver transplant recipients 6 months after coronavirus disease 2019 (COVID-19) resolution. A total of 71 liver transplant recipients were matched with 71 immunocompetent controls by a propensity score including variables with a well-known prognostic impact in COVID-19. Paired case–control serological data were also available in 62 liver transplant patients and 62 controls at month 3 after COVID-19. Liver transplant recipients showed a lower incidence of anti-nucleocapsid IgG antibodies at 3 months (77.4% vs. 100%, p < .001) and at 6 months (63.4% vs. 90.1%, p < .001). Lower levels of antibodies were also observed in liver transplant patients at 3 (p = .001) and 6 months (p < .001) after COVID-19. In transplant patients, female gender (OR = 13.49, 95% CI: 2.17–83.8), a longer interval since transplantation (OR = 1.19, 95% CI: 1.03–1.36), and therapy with renin–angiotensin–aldosterone system inhibitors (OR = 7.11, 95% CI: 1.47–34.50) were independently associated with persistence of antibodies beyond 6 months after COVID-19. Therefore, as compared with immunocompetent patients, liver transplant recipients show a lower prevalence of anti-SARS-CoV-2 antibodies and more pronounced antibody levels decline. 相似文献
76.
77.
Tarek Alhamad Michelle Lubetzky Krista L. Lentine Emmanuel Edusei Ronald Parsons Martha Pavlakis Kenneth J. Woodside Deborah Adey Christopher D. Blosser Beatrice P. Concepcion John Friedewald Alexander Wiseman Neeraj Singh Su-Hsin Chang Gaurav Gupta Miklos Z. Molnar Arpita Basu Edward Kraus Song Ong Arman Faravardeh Ekamol Tantisattamo Leonardo Riella Jim Rice Darshana M. Dadhania 《American journal of transplantation》2021,21(9):3034-3042
Kidney allograft failure and return to dialysis carry a high risk of morbidity. A practice survey was developed by the AST Kidney Pancreas Community of Practice workgroup and distributed electronically to the AST members. There were 104 respondents who represented 92 kidney transplant centers. Most survey respondents were transplant nephrologists at academic centers. The most common approach to immunosuppression management was to withdraw the antimetabolite first (73%), while only 12% responded they would withdraw calcineurin inhibitor (CNI) first. More than 60% reported that the availability of a living donor is the most important factor in their decision to taper immunosuppression, followed by risk of infection, risk of sensitization, frailty, and side effects of medications. More than half of respondents reported that embolization was either not available or offered to less than 10% as an option for surgical intervention. Majority reported that ≤50% of failed allograft patients were re-listed before dialysis, and less than a quarter of transplant nephrologists performed frequent visits with their patients with failed kidney allograft after they return to dialysis. This survey demonstrates heterogeneity in the care of patients with a failing allograft and the need for more evidence to guide improvements in clinical practice related to transition of care. 相似文献
78.
Suk Kyun Hong Dongkyu Han Sun-Kyung Lee Jiyeon Kim Eung-Soo Hwang Haeryoung Kim Jae-Il Lee Kwangpyo Hong Eui Soo Han Jae-Hyung Cho Jeong-Moo Lee YoungRok Choi Kwang-Woong Lee Nam-Joon Yi Jaeseok Yang Kyung-Suk Suh 《American journal of transplantation》2021,21(9):2978-2991
Tolerance induction remains challenging following liver transplantation and the long-term use of immunosuppressants, especially calcineurin inhibitors, leads to serious complications. We aimed to test an alternative immunosuppressant, a chimeric anti-ICAM-1 monoclonal antibody, MD-3, for improving the outcomes of liver transplantation. We used a rhesus macaque liver transplantation model and monkeys were divided into three groups: no immunosuppression (n = 2), conventional immunosuppression (n = 4), and MD-3 (n = 5). Without immunosuppression, liver allografts failed within a week by acute rejection. Sixteen-week-long conventional immunosuppression that consisted of prednisolone, tacrolimus, and an mTOR inhibitor prolonged liver allograft survival; however, recipients died of acute T cell–mediated rejection (day 52), chronic rejection (days 62 and 66), or adverse effects of mTOR inhibitor (day 32). In contrast, 12-week-long MD-3 therapy with transient conventional immunosuppression in the MD-3 group significantly prolonged the survival of liver allograft recipients (5, 96, 216, 412, 730 days; p = .0483). MD-3 effectively suppressed intragraft inflammatory cell infiltration, anti-donor T cell responses, and donor-specific antibody with intact anti-cytomegalovirus antibody responses. However, this regimen ended in chronic rejection. In conclusion, short-term therapy with MD-3 markedly improved liver allograft survival to 2 years without maintenance of immunosuppressant. MD-3 is therefore a promising immune-modulating agent for liver transplantation. 相似文献
79.
Jiang Bian Ting Wang Jijun Sun Xiaozhen He Zhijiao Wu Songmei Zhang Hao Chi Tingting Fan Shaowen Wang Weiyun Shi Qingguo Ruan 《American journal of transplantation》2021,21(12):3858-3870
The relevance of Tregs in the induction of tolerance against corneal allografts has been well established. Although it is well known that the conversion of Tregs into effector-like cells contributes to the loss of corneal immune privilege, the underlying mechanism is still not fully understood. Using heterologous penetrating keratoplasty model, we found that Tregs from corneal allograft rejected mice (inflam-Tregs) exhibit impaired function and characteristics of effector T cells. Further study showed that the expression of NF-κB c-Rel, a key mediator of effector T cell function, was significantly increased in inflam-Tregs. Mechanistic study revealed that elevated NF-κB c-Rel level in inflam-Tregs impaired Treg function through the promotion of inflammatory cytokine production and glycolysis. More importantly, we demonstrated that targeting NF-κB c-Rel was able to improve the immune suppressive function of inflam-Tregs in vitro and enhance the potential of them to suppress corneal transplantation rejection. Therefore, our current study identified NF-κB c-Rel as a key mediator of the conversion of Tregs into effector-like cells when under inflammatory environment. 相似文献