全文获取类型
收费全文 | 118161篇 |
免费 | 12380篇 |
国内免费 | 6585篇 |
专业分类
耳鼻咽喉 | 838篇 |
儿科学 | 1337篇 |
妇产科学 | 1491篇 |
基础医学 | 32267篇 |
口腔科学 | 3417篇 |
临床医学 | 8019篇 |
内科学 | 16877篇 |
皮肤病学 | 2285篇 |
神经病学 | 8361篇 |
特种医学 | 2188篇 |
外国民族医学 | 25篇 |
外科学 | 9568篇 |
综合类 | 17675篇 |
现状与发展 | 30篇 |
一般理论 | 2篇 |
预防医学 | 3857篇 |
眼科学 | 3032篇 |
药学 | 11557篇 |
23篇 | |
中国医学 | 4182篇 |
肿瘤学 | 10095篇 |
出版年
2024年 | 256篇 |
2023年 | 1692篇 |
2022年 | 3085篇 |
2021年 | 4283篇 |
2020年 | 3918篇 |
2019年 | 3402篇 |
2018年 | 3430篇 |
2017年 | 4052篇 |
2016年 | 4537篇 |
2015年 | 4948篇 |
2014年 | 7328篇 |
2013年 | 9231篇 |
2012年 | 7006篇 |
2011年 | 8028篇 |
2010年 | 6574篇 |
2009年 | 6247篇 |
2008年 | 6478篇 |
2007年 | 6443篇 |
2006年 | 5986篇 |
2005年 | 5129篇 |
2004年 | 4346篇 |
2003年 | 3568篇 |
2002年 | 2796篇 |
2001年 | 2425篇 |
2000年 | 2041篇 |
1999年 | 1783篇 |
1998年 | 1677篇 |
1997年 | 1551篇 |
1996年 | 1402篇 |
1995年 | 1458篇 |
1994年 | 1299篇 |
1993年 | 1122篇 |
1992年 | 934篇 |
1991年 | 922篇 |
1990年 | 750篇 |
1989年 | 737篇 |
1988年 | 639篇 |
1987年 | 617篇 |
1986年 | 520篇 |
1985年 | 770篇 |
1984年 | 700篇 |
1983年 | 479篇 |
1982年 | 610篇 |
1981年 | 439篇 |
1980年 | 371篇 |
1979年 | 329篇 |
1978年 | 220篇 |
1977年 | 172篇 |
1976年 | 155篇 |
1975年 | 58篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
11.
Osric A. Forrest Daniel M. Chopyk Yael Gernez Milton R. Brown Carol K. Conrad Richard B. Moss Vin Tangpricha Limin Peng Rabindra Tirouvanziam 《Journal of cystic fibrosis》2019,18(1):64-70
Background
Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.Methods
Resistin levels were measured in plasma and sputum from three retrospective CF cohorts spanning a wide range of disease. We also assessed the ability of neutrophils to secrete resistin upon activation in vitro. Finally, we constructed a multivariate model assessing the relationship between resistin levels and lung function.Results
Plasma resistin levels were only marginally higher in CF than in healthy control subjects. By contrast, sputum resistin levels were very high in CF, reaching 50–100 fold higher levels than in plasma. Among CF patients, higher plasma resistin levels were associated with allergic bronchopulmonary aspergillosis, and higher sputum resistin levels were associated with CF-related diabetes. Mechanistically, in vitro release of neutrophil primary granules was concomitant with resistin secretion. Overall, sputum resistin levels were negatively correlated with CF lung function, independently of other variables (age, sex, and genotype).Conclusions
Our data establish relationships between resistin levels in the plasma and sputum of CF patients that correlate with disease status, and identify resistin as a novel mechanistic link between neutrophilic inflammation and lung disease in CF. 相似文献12.
《Biomedical and environmental sciences : BES》2020,33(5):295-305
Objective Interferon-induced transmembrane protein 3(IFITM3) is an important member of the IFITM family. However, the molecular mechanisms underlying its antiviral action have not been completely elucidated. Recent studies on IFITM3, particularly those focused on innate antiviral defense mechanisms, have shown that IFITM3 affects the body's adaptive immune response. The aim of this study was to determine the contribution of IFITM3 proteins to immune control of influenza infection in vivo.Methods We performed proteomics, flow cytometry, and immunohistochemistry analysis and used bioinformatics tools to systematically compare and analyze the differences in natural killer(NK) cell numbers, their activation, and their immune function in the lungs of Ifitm3-/-and wild-type mice.Results Ifitm3-/-mice developed more severe inflammation and apoptotic responses compared to wild-type mice. Moreover, the NK cell activation was higher in the lungs of Ifitm3-/-mice during acute influenza infection.Conclusions Based on our results, we speculate that the NK cells are more readily activated in the absence of IFITM3, increasing mortality in Ifitm3-/-mice. 相似文献
13.
Many nanoparticles (NPs) have toxic effects on multiple cell lines. This toxicity is assumed to be related to their accumulation within cells. However, the process of internalization of NPs has not yet been fully characterized. In this study, the cellular uptake, accumulation, and localization of titanium dioxide nanoparticles (TiO2 NPs) in rat (C6) and human (U373) glial cells were analyzed using time-lapse microscopy (TLM) and transmission electron microscopy (TEM). Cytochalasin D (Cyt-D) was used to evaluate whether the internalization process depends of actin reorganization. To determine whether the NP uptake is mediated by phagocytosis or macropinocytosis, nitroblue tetrazolium (NBT) reduction was measured and the 5-(N-ethyl-N-isopropyl)-amiloride was used. Expression of proteins involved with endocytosis and exocytosis such as caveolin-1 (Cav-1) and cysteine string proteins (CSPs) was also determined using flow cytometry.TiO2 NPs were taken up by both cell types, were bound to cellular membranes and were internalized at very short times after exposure (C6, 30 min; U373, 2 h). During the uptake process, the formation of pseudopodia and intracellular vesicles was observed, indicating that this process was mediated by endocytosis. No specific localization of TiO2 NPs into particular organelles was found: in contrast, they were primarily localized into large vesicles in the cytoplasm. Internalization of TiO2 NPs was strongly inhibited by Cyt-D in both cells and by amiloride in U373 cells; besides, the observed endocytosis was not associated with NBT reduction in either cell type, indicating that macropinocytosis is the main process of internalization in U373 cells. In addition, increases in the expression of Cav-1 protein and CSPs were observed.In conclusion, glial cells are able to internalize TiO2 NPs by a constitutive endocytic mechanism which may be associated with their strong cytotoxic effect in these cells; therefore, TiO2 NPs internalization and their accumulation in brain cells could be dangerous to human health. 相似文献
14.
Jinju Wang Shuzhen Chen Wenfeng Zhang Yanfang Chen Ji C. Bihl 《CNS Neuroscience & Therapeutics》2020,26(12):1255
AimsWe previously showed that the protective effects of endothelial progenitor cells (EPCs)‐released exosomes (EPC‐EXs) on endothelium in diabetes. However, whether EPC‐EXs are protective in diabetic ischemic stroke is unknown. Here, we investigated the effects of EPC‐EXs on diabetic stroke mice and tested whether miR‐126 enriched EPC‐EXs (EPC‐EXsmiR126) have enhanced efficacy.MethodsThe db/db mice subjected to ischemic stroke were intravenously administrated with EPC‐EXs 2 hours after ischemic stroke. The infarct volume, cerebral microvascular density (MVD), cerebral blood flow (CBF), neurological function, angiogenesis and neurogenesis, and levels of cleaved caspase‐3, miR‐126, and VEGFR2 were measured on day 2 and 14.ResultsWe found that (a) injected EPC‐EXs merged with brain endothelial cells, neurons, astrocytes, and microglia in the peri‐infarct area; (b) EPC‐EXsmiR126 were more effective than EPC‐EXs in decreasing infarct size and increasing CBF and MVD, and in promoting angiogenesis and neurogenesis as well as neurological functional recovery; (c) These effects were accompanied with downregulated cleaved caspase‐3 on day 2 and vascular endothelial growth factor receptor 2 (VEGFR2) upregulation till day 14.ConclusionOur results indicate that enrichment of miR126 enhanced the therapeutic efficacy of EPC‐EXs on diabetic ischemic stroke by attenuating acute injury and promoting neurological function recovery. 相似文献
15.
《Vaccine》2022,40(11):1594-1605
In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes. 相似文献
16.
Hsiao-Hsuan Kuo Ran Fan Nina Dvorina Andres Chiesa-Vottero William M. Baldwin III 《Journal of the American Society of Nephrology : JASN》2015,26(4):855-863
Antibody-mediated rejection is a major complication in renal transplantation. The pathologic manifestations of acute antibody-mediated rejection that has progressed to functional impairment of a renal transplant have been defined in clinical biopsy specimens. However, the initial stages of the process are difficult to resolve with the unavoidable variables of clinical studies. We devised a model of renal transplantation to elucidate the initial stages of humoral rejection. Kidneys were orthotopically allografted to immunodeficient mice. After perioperative inflammation subsided, donor-specific alloantibodies were passively transferred to the recipient. Within 1 hour after a single transfer of antibodies, C4d was deposited diffusely on capillaries, and von Willebrand factor released from endothelial cells coated intravascular platelet aggregates. Platelet-transported inflammatory mediators platelet factor 4 and serotonin accumulated in the graft at 100- to 1000-fold higher concentrations compared with other platelet-transported chemokines. Activated platelets that expressed P-selectin attached to vascular endothelium and macrophages. These intragraft inflammatory changes were accompanied by evidence of acute endothelial injury. Repeated transfers of alloantibodies over 1 week sustained high levels of platelet factor 4 and serotonin. Platelet depletion decreased platelet mediators and altered the accumulation of macrophages. These data indicate that platelets augment early inflammation in response to donor-specific antibodies and that platelet-derived mediators may be markers of evolving alloantibody responses. 相似文献
17.
目的评估血肌酐和尿常规的常规检测基础上联合血清胱抑素C和尿微量白蛋白检测在人类免疫缺陷病毒(HIV)感染者肾功能损伤检测中的应用价值。
方法以2019年2~5月于首都医科大学附属北京地坛医院感染一科住院的169例HIV感染者为研究对象,完善其尿常规、尿微量白蛋白、血肌酐、血清胱抑素C检测;分析尿蛋白及尿微量白蛋白的阳性检出率及其差异,血肌酐升高及血清胱抑素C升高的比例及其差异。计算应用替诺福韦酯(TDF)及合并丙型肝炎、高血压、糖尿病、肿瘤的肾功能损伤的相对危险度。
结果169例HIV感染者中尿常规示尿蛋白阳性者5例(3.0%),尿微量白蛋白升高者17例(10.1%),两者阳性检出率差异具有统计学意义(χ2 = 5.9、P = 0.007)。血肌酐升高者10例(5.9%),血清胱抑素C升高者20例(11.8%),两者阳性检出率差异具有统计学意义(χ2 = 3.0、P = 0.042)。在尿常规和血肌酐检测的基础上联合检测尿微量白蛋白和血清胱抑素C的总体阳性检出率为49例(30.0%)。CD4+ T淋巴细胞计数< 200个/μl与≥ 200个/μl组患者血清胱抑素C水平分别为0.94(0.83,1.05)mg/L、0.85(0.77,0.95)mg/L,差异具有统计学意义(Z =-3.02、P = 0.003)。应用TDF及合并丙型肝炎、高血压、糖尿病、肿瘤的肾功能损伤的相对危险度分别为1.1、1.5、1.9、2.2和1.4。
结论HIV感染者中,单纯以尿常规为依据评估有无蛋白尿,以血肌酐水平为依据评估肾小球滤过功能会低估肾功能损伤的患病率。在常规检测血肌酐和尿常规的基础上联合检测血清胱抑素C和尿微量白蛋白在提高HIV感染者肾功能损伤检出率方面具有重要的应用价值。低CD4+ T淋巴细胞计数、应用TDF及合并丙型肝炎、高血压、糖尿病、肿瘤均为肾功能损伤的危险因素。 相似文献
18.
Objective: To assess the effect of electroacupuncture(EA) on expression of cytoskeletal proteins from Sertoli cells(SCs) and spermatogenesis in rats with oligozoospermia of insufficiency of Shen(Kidney)essence syndrome(OIKES).Methods: Twenty healthy male Sprague-Dawley rats were randomly assigned to four groups using a random number table: control,tripterygium glycosides(TG) treatment,sham and EA groups(n=5 in each group).A rat model of OIKES was established by oral gavage with TG.The EA group was treated with TG and received EA at Shenshu(BL 23) and Zusanli(ST 36) acupoints for 20 min,once daily for 30 days,while the sham group received EA at identical acupoints with skin penetration without stimulation.After 30 days,the ?nal body weight and coef?cients for the testis and epididymis were calculated and sperm parameters were measured.Immunohistochemical analyses were performed to detect expression of vimentin and α-tubulin in SCs and proliferating cell nuclear antigen(PCNA) immunoreactivity in germ cells.Apoptosis in germ cells was quanti?ed by the transferase biotin-dUTP nick end labeling assay.Results: Compared with the control group,the final body weight and testis/epididymis coefficients of rats in the TG-treated group were not significantly different,but the sperm count and motility were lower(P0.05).Expressions of vimentin and α-tubulin were also signi?cantly weaker(P0.01).The PCNA immunoreactivity of germ cells was decreased(P=0.059),whereas the apoptotic index of germ cells was increased signi?cantly(P0.01).In contrast,EA at BL 23 and ST 36 acupoints signi?cantly improved the ?nal body weight as well as the sperm count,concentration and motility(P0.01 or P0.05).EA increased expression of vimentin and α-tubulin in SCs markedly,and signi?cantly enhanced PCNA immunoreactivity with decreased apoptosis in germ cells(P0.01 or P0.05).Conclusions: EA at BL 23 and ST 36 acupoints has protective effects on spermatogenesis in rats with OIKES.This effect seems to be achieved by attenuating TG-induced disruption of cytoskeletal protein in SCs. 相似文献
19.
20.
Alejandra Gordillo Hernández Eduardo Dominguez-Adame Lanuza Auxiliadora Cano Matias Rosario Perez Huertas Katherine Maria Gallardo Rodriguez Purificacion Gallinato Perez Fernando Oliva Mompean 《World journal of gastrointestinal surgery》2015,7(8):170-173
Gangliocytic paragangliomas are rare tumors that almost exclusively occur within the second portion of the duodenum. Although these tumors generally have a benign clinical course, they have the potential to recur or metastasize to regional lymph nodes. The case report presented here describes a 57-year-old female patient with melena, progressive asthenia, anemia, and a mass in the second-third portion of the duodenum that was treated by local excision. The patient was diagnosed with a friable bleeding tumor. The histologic analysis showed that the tumor was a 4 cm gangliocytic paraganglioma without a malignant cell pattern. In the absence of local invasion or distant metastasis, endoscopic resection represents a feasible, curative therapy. Although endoscopic polypectomy is currently considered the treatment of choice, it is not recommended if the size of the tumor is > 3 cm and/or there is active or recent bleeding. Patients diagnosed with a gangliocytic paraganglioma should be closely followed-up for possible local recurrence. 相似文献