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11.
《The Egyptian Rheumatologist》2022,44(4):377-380
BackgroundRheumatoid arthritis (RA) is the most common type of inflammatory arthritis. Newly emerging evidence has highlighted the role of B-cell produced cytokines in the development and progression of RA. Specifically, the expression of IL-40 has been shown to be significantly increased in affected patients.Patients and methodsThe study included 66 patients attending Rheumatology Unit, Baghdad Teaching Hospital and 66 matched controls. C-reactive protein (CRP), rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) were measured. Disease activity score (DAS28) was assessed. Serum IL-40 levels were assessed using an enzyme-linked immunosorbent assay (ELISA).ResultsThe mean ages of patients were 46.5 ± 10.2 years (23–68 years) and were 55 females and 11 males (F:M 5:1). 4 were smokers. Positivity of CRP, RF and anti-CCP were 75.8 %, 65.2 % and 62.2 % respectively. Steroids were received by 21.2 %, methotrexate by 56.1 %, biologics in the form of etanercept and adalimumab by 86.4 %. IL-40 was significantly higher in patients (9.1 ± 1.3 ng/ml) than in controls (7.5 ± 2.2 ng/ml; p < 0.001). The IL-40 level was comparable between females and males and was not related to smoking, CRP, RF or anti-CCP positivity or to receiving medications. Serum IL-40 showed good validity in diagnosing RA at a cut-off value (≥8.2 ng/ml) and area under curve (AUC) (0.74), the sensitivity was 73.2 %, specificity (66.7 %), and the accuracy (70.5 %)(p < 0.001).ConclusionThe increased level of serum IL-40 and its potential diagnostic role have been revealed in RA. Further studies are needed to be implement and elucidate the complete role of IL-40 in RA. 相似文献
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13.
Dong‐Jie Li Jie Tong Yong‐Hua Li Hong‐Bo Meng Qing‐Xin Ji Guo‐Yan Zhang Jia‐Hui Zhu Wen‐Jing Zhang Fei‐Yan Zeng Gang Huang Xia Hua Fu‐Ming Shen Pei Wang 《Journal of pineal research》2019,67(4)
Melatonin has been previously shown to prevent nonalcoholic fatty liver disease (NAFLD), yet the underlying mechanisms are poorly understood. Here, we identified a previously unknown regulatory action of melatonin on apoptosis signal‐regulating kinase 1 (ASK1) signaling pathway in the pathogenesis and development of NAFLD. Although melatonin administration did not alter food intake, it significantly alleviated fatty liver phenotypes, including the body weight gain, insulin resistance, hepatic lipid accumulation, steatohepatitis, and fibrosis in a high‐fat diet (HFD)‐induced NAFLD mouse model (in vivo). The protection of melatonin against NAFLD was not affected by inactivation of Kupffer cell in this model. In NAFLD mice liver, ASK1 signal cascade was substantially activated, evidence by the enhancement of total ASK1, phospho‐ASK1, phospho‐MKK3/6, phospho‐p38, phospho‐MKK4/7, and phospho‐JNK. Melatonin treatment significantly suppressed the ASK1 upregulation and the phosphorylation of ASK1, MKK3/6, MKK4/7, p38, and JNK. Mechanistically, we found that lipid stress triggered the interaction between ASK1 and TNF receptor‐associated factors (TRAFs), including TRAF1, TRAF2, and TRAF6, which resulted in ASK1 deubiquitination and thereby increased ASK1 protein stability. Melatonin did not alter ASK1 mRNA level; however, it activated a scaffold protein β‐arrestin‐1 and enabled it to bind to ASK1, which antagonized the TRAFs‐mediated ASK1 deubiquitination, and thus reduced ASK1 protein stability. Consistent with these findings, knockout of β‐arrestin‐1 in mice partly abolished the protection of melatonin against NAFLD. Taken together, our results for the first time demonstrate that melatonin safeguards against NAFLD by eliminating ASK1 activation via inhibiting TRAFs‐mediated ASK1 deubiquitination and stabilization in a β‐arrestin‐1 dependent manner. 相似文献
14.
Yueh-Ling Hsieh Ming-Ta Lin Chang-Zern Hong Hsin-Shui Chen 《Foot and Ankle Surgery》2019,25(2):186-192
Background
This study investigated the effects of percutaneous soft tissue release (PSTR) performed using a blunt cannula on (1) the inflammatory cells-count, (2) expressions of calcitonin gene-related peptide (CGRP) and (3) substance P (SP) in rabbits with chronic phase of collagenase-induced Achilles tendinopathy.Methods
Thirty-two adult male New Zealand rabbits were randomly divided into four groups: (1) collagenase and PSTR treatment; (2) collagenase and sham-operated PSTR treatment; (3) vehicle-only injection and PSTR treatment; and (4) vehicle-only injection and sham-operated PSTR treatment. Achilles tendon of adult male rabbits was injected with 10 μl of collagenase under ultrasonography localization. After 30 days, PSTR was performed using an 18G beauty cosmetic blunt tip micro cannula needle to release the soft tissue and paratenon above the inflamed Achilles tendon. The treated tendons and spinal cords of L5-S2 were harvested 5 days after treatment for histological assessment and immunohistochemical analysis.Results
Histopathological examination revealed that PSTR achieved significant reduction in hypercellularity with pronounced infiltration of immune cells at the site of paratenon in tendons injected with collagenase compared with sham operation (p < 0.05). Immunohistochemical analysis also showed marked decrease in expression of CGRP in tendon and SP in dorsal horns after PSTR (p < 0.05).Conclusions
This study showed positive effects in an animal model of chronic tendinopathy, and can be considered a treatment option, but that further research is necessary to determine its role in clinical practice. 相似文献15.
16.
目的 探讨口服硝酸盐对大鼠背部随意皮瓣的影响,以硝酸盐-亚硝酸盐-NO通路为切入点,探讨其可能的机制。方法 将24只雄性Wistar大鼠随机分为硝酸盐组、氯化钠组和对照组,每组8只。采用改良大鼠背部随意皮瓣制作方法造模。硝酸盐干预组在术前7 d及术后每天口服0.5 mmol/L硝酸钠,氯化钠组每天口服等量氯化钠,对照组每天口服蒸馏水。术后第7天,检测各组皮瓣的存活情况,大鼠血清中硝酸盐、亚硝酸盐、肿瘤坏死因子(tumor necrosis factor alpha,TNF-a)和白介素6(interleukin-6,IL-6)水平,以及皮瓣组织中超氧化物歧化酶(superoxide dismutase,SOD)和丙二醛(malondialdehyde,MDA)水平。采用SPSS 20.0软件包对数据进行t检验。结果 硝酸盐组皮瓣的存活面积显著高于对照组(P<0.05)。H-E染色显示,硝酸盐明显减轻了皮瓣的组织学损伤。硝酸钠显著增加了血清中硝酸盐和亚硝酸盐水平(P<0.05),并显著下调血清中TNF-a和IL-6水平(P<0.05)。此外,硝酸盐组皮瓣组织内MDA表达显著减少(P<0.05),SOD表达显著增加(P<0.05)。结论 口服硝酸盐可通过调控皮瓣的氧化应激和炎症反应保护皮瓣。 相似文献
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18.
《Pancreatology》2022,22(7):880-886
BackgroundPremature intracellular trypsinogen activation has long been considered a key initiator of acute pancreatitis (AP). Cathepsin B (CTSB) activates trypsinogen, while cathepsin L (CTSL) inactivates trypsin(ogen), and both proteins play a role in the onset of AP.MethodsAP was induced by 7 hourly intraperitoneal injections of cerulein (50 μg/kg) in wild-type and pancreas-specific conditional Ctsb knockout (CtsbΔpan), Ctsl knockout (CtslΔpan), and Ctsb;Ctsl double-knockout (CtsbΔpan;CtslΔpan) mice. Pancreatic samples were collected and analyzed by histology, immunohistochemistry, real-time PCR, and immunoblots. Trypsin activity was measured in pancreatic homogenates. Peripheral blood was collected, and serum amylase activity was measured.ResultsDouble deletion of Ctsb and Cstl did not affect pancreatic development or mouse growth. After 7 times cerulein injections, double Ctsb and Ctsl deficiency in mouse pancreases increased trypsin activity to the same extent as that in Ctsl-deficient mice, while Ctsb deficiency decreased trypsin activity but did not affect the severity of AP. CtsbΔpan;CtslΔpan mice had comparable serum amylase activity and histopathological changes and displayed similar levels of proinflammatory cytokines, apoptosis, and autophagy activity compared with wild-type, CtsbΔpan, and CtslΔpan mice.ConclusionDouble deletion of Ctsb and Ctsl in the mouse pancreas altered intrapancreatic trypsin activity but did not affect disease severity and inflammatory response after cerulein-induced AP. 相似文献
19.
Molecules such as cytokines, energetic substrates, and hormones found in the immune cell environment, especially lymphocytes and monocytes, are crucial for directing energy metabolism. In turn, changes in energy metabolism occur in a synchronized manner with the activation of certain signaling pathways, thereby this crosstalk is responsible for determining the functionality of immune cells. The immunometabolism field has grown over time and that is becoming increasingly promising in several populations; here we discuss the mechanisms involved in sedentary and physically active middle-aged individuals and master athletes. In this context, this review shows that the physical activity status and lifelong exercise seems to be good strategies for the promotion of metabolic and functional adaptations in T lymphocytes and monocytes, counteracting inflammatory environments caused by expanded adipose tissue and sedentary behavior, as well as delaying the immunosenescence caused by aging. 相似文献
20.
Human aging is a multifactorial phenomenon that affects numerous organ systems and cellular processes, with the immune system being one of the most dysregulated. Immunosenescence, the gradual deterioration of the immune system, and inflammaging, a chronic inflammatory state that persists in the elderly, are among the plethora of immune changes that occur during aging. Almost all populations of immune cells change with age in terms of numbers and/or activity. These alterations are in general highly detrimental, resulting in an increased susceptibility to infections, reduced healing abilities, and altered homeostasis that promote the emergence of age-associated diseases such as cancer, diabetes, and other diseases associated with inflammation. Thanks to recent developments, several strategies have been proposed to target central immunological processes or specific immune subpopulations affected by aging. These therapeutic approaches could soon be applied in the clinic to slow down or even reverse specific age-induced immune changes in order to rejuvenate the immune system and prevent or reduce the impact of various diseases. Due to its systemic nature and interconnection with all the other systems in the body, the immune system is an attractive target for aging intervention because relatively targeted modifications to a small set of cells have the potential to improve the health of multiple organ systems. Therefore, anti-aging immune targeting therapies could represent a potent approach for improving healthspan. Here, we review aging changes in the major components of the immune system, we summarize the current immune-targeting therapeutic approaches in the context of aging and discuss the future directions in the field of immune rejuvenation. 相似文献