全文获取类型
收费全文 | 6202篇 |
免费 | 377篇 |
国内免费 | 229篇 |
专业分类
耳鼻咽喉 | 33篇 |
儿科学 | 84篇 |
妇产科学 | 20篇 |
基础医学 | 980篇 |
口腔科学 | 556篇 |
临床医学 | 375篇 |
内科学 | 638篇 |
皮肤病学 | 79篇 |
神经病学 | 306篇 |
特种医学 | 89篇 |
外科学 | 785篇 |
综合类 | 519篇 |
现状与发展 | 1篇 |
预防医学 | 295篇 |
眼科学 | 31篇 |
药学 | 1638篇 |
4篇 | |
中国医学 | 210篇 |
肿瘤学 | 165篇 |
出版年
2023年 | 46篇 |
2022年 | 74篇 |
2021年 | 158篇 |
2020年 | 161篇 |
2019年 | 181篇 |
2018年 | 197篇 |
2017年 | 168篇 |
2016年 | 160篇 |
2015年 | 154篇 |
2014年 | 445篇 |
2013年 | 442篇 |
2012年 | 383篇 |
2011年 | 439篇 |
2010年 | 379篇 |
2009年 | 334篇 |
2008年 | 279篇 |
2007年 | 263篇 |
2006年 | 260篇 |
2005年 | 232篇 |
2004年 | 204篇 |
2003年 | 171篇 |
2002年 | 167篇 |
2001年 | 123篇 |
2000年 | 85篇 |
1999年 | 89篇 |
1998年 | 73篇 |
1997年 | 72篇 |
1996年 | 70篇 |
1995年 | 54篇 |
1994年 | 47篇 |
1993年 | 39篇 |
1992年 | 41篇 |
1991年 | 35篇 |
1990年 | 40篇 |
1989年 | 40篇 |
1988年 | 32篇 |
1987年 | 34篇 |
1986年 | 27篇 |
1985年 | 84篇 |
1984年 | 86篇 |
1983年 | 84篇 |
1982年 | 77篇 |
1981年 | 57篇 |
1980年 | 51篇 |
1979年 | 52篇 |
1978年 | 28篇 |
1977年 | 24篇 |
1976年 | 21篇 |
1975年 | 14篇 |
1973年 | 15篇 |
排序方式: 共有6808条查询结果,搜索用时 15 毫秒
1.
《Saudi Pharmaceutical Journal》2022,30(5):595-604
Anthrax is a zoonotic infection caused by the gram-positive, aerobic, spore-forming bacterium Bacillus anthracis. Depending on the origin of the infection, serious health problems or mortality is possible. The virulence of B. anthracis is reliant on three pathogenic factors, which are secreted upon infection: protective antigen (PA), lethal factor (LF), and edema factor (EF). Systemic illness results from LF and EF entering cells through the formation of a complex with the heptameric form of PA, bound to the membrane of infected cells through its receptor. The currently available anthrax vaccines have multiple drawbacks, and recombinant PA is considered a promising second-generation vaccine candidate. However, the inherent chemical instability of PA through Asn deamidation at multiple sites prevents its use after long-term storage owing to loss of potency. Moreover, there is a distinct possibility of B. anthracis being used as a bioweapon; thus, the developed vaccine should remain efficacious and stable over the long-term. Second-generation anthrax vaccines with appropriate adjuvant formulations for enhanced immunogenicity and safety are desired. In this article, using protein engineering approaches, we have reviewed the stabilization of anthrax vaccine candidates that are currently licensed or under preclinical and clinical trials. We have also proposed a formulation to enhance recombinant PA vaccine potency via adjuvant formulation. 相似文献
2.
《药学学报(英文版)》2020,10(5):799-811
Overexpression of adenosine triphosphate (ATP)-binding cassette subfamily G member 2 (ABCG2) in cancer cells is known to cause multidrug resistance (MDR), which severely limits the clinical efficacy of chemotherapy. Currently, there is no FDA-approved MDR modulator for clinical use. In this study, rociletinib (CO-1686), a mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was found to significantly improve the efficacy of ABCG2 substrate chemotherapeutic agents in the transporter-overexpressing cancer cells in vitro and in MDR tumor xenografts in nude mice, without incurring additional toxicity. Mechanistic studies revealed that in ABCG2-overexpressing cancer cells, rociletinib inhibited ABCG2-mediated drug efflux and increased intracellular accumulation of ABCG2 probe substrates. Moreover, rociletinib, inhibited the ATPase activity, and competed with [125I] iodoarylazidoprazosin (IAAP) photolabeling of ABCG2. However, ABCG2 expression at mRNA and protein levels was not altered in the ABCG2-overexpressing cells after treatment with rociletinib. In addition, rociletinib did not inhibit EGFR downstream signaling and phosphorylation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK). Our results collectively showed that rociletinib reversed ABCG2-mediated MDR by inhibiting ABCG2 efflux function, thus increasing the cellular accumulation of the transporter substrate anticancer drugs. The findings advocated the combination use of rociletinib and other chemotherapeutic drugs in cancer patients with ABCG2-overexpressing MDR tumors. 相似文献
3.
《Clinical therapeutics》2019,41(10):2066-2072.e2
PurposeAortic stenosis is a common cause of valvular heart disease with no means of prevention. The recognized association between aortic stenosis and serum phosphate raises the possibility of preventing progression of the disorder by using phosphate-binding drugs, but there is uncertainty whether such treatment lowers serum phosphate levels in patients without diagnosed renal failure. This pilot study was conducted to answer this question in patients with aortic stenosis.MethodsA randomized, double-blind, crossover trial of the phosphate-binding drug sevelamer was conducted in 72 patients. Patients were prescribed sevelamer 0.8 g (low-dose), sevelamer 2.4 g (high-dose), and matching placebo, 3 times daily with food; each regimen lasted 6 weeks and was allocated at random. Serum phosphate levels were measured at the end of each treatment period, and within-person levels were compared.FindingsSixty-one patients completed the 3 treatment periods. There was no significant difference in the mean end-treatment phosphate levels across all patients (3.38, 3.36, and 3.31 mg/dL with placebo, low-dose sevelamer, and high-dose sevelamer, respectively). Post hoc analysis showed a reduction in phosphate levels with increasing sevelamer dose in the highest baseline phosphate quartile group; a 0.3 mg/dL reduction (mean, 4.09 mg/dL with placebo, 3.95 mg/dL with low-dose sevelamer, and 3.79 mg/dL with high-dose sevelamer; Ptrend = 0.027).ImplicationsSevelamer had no overall statistically significant effect in lowering serum phosphate levels, but a reduction was observed in patients with phosphate levels in the highest quartile group of the population distribution. This hypothesis-generating result requires confirmation in an independent study. If confirmed, a trial of sevelamer in preventing the progression of aortic stenosis may be justified in patients with high phosphate levels. ISRCTN Registry identifier: ISRCTN17365679. 相似文献
4.
《The Knee》2021
BackgroundThis study compared bone union progression using highly porous (80% porosity) β-tricalcium phosphate (β-TCP) granules or allogeneic bone chips in the gap created by medial opening-wedge high tibial osteotomy (MOWHTO).MethodsThe study population consisted of 54 patients who received MOWHTO with locking plate fixation: 27 patients using highly porous β-TCP granules, and 27 age- and sex-matched patients using allogeneic bone chips. Bone union progression was evaluated 1, 3, 6, and 12 months postoperatively. The presence of radiographic sclerosis at the osteotomy margin was also assessed.ResultsAmong all patients, the highest degree of bone union observed 12 months postoperatively was grade 4. As postoperative time passed, bone union progression of highly porous β-TCP granules increased linearly and was statistically significant compared with that of cancellous allogeneic bone chips (P = 0.014). The presence of radiographic sclerosis at the osteotomy margin was significantly less common in the β-TCP group than in the allograft group (P = 0.003) and was the strongest predictor of delayed progress of bone union (odds ratio = 6.16, P = 0.006).ConclusionsPatients who underwent MOWHTO using highly porous β-TCP granules had faster new bone remodeling, less radiographic sclerosis at the osteotomy margin, and no inferior clinical outcome compared with allogeneic bone chips, as determined at the 1-year follow up. The presence of radiographic sclerosis at the osteotomy margin in patients undergoing MOWHTO using allogeneic bone or synthetic bone substitute may indicate delayed progress of bone union. 相似文献
5.
6.
7.
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
8.
目的:应用Logistic模型和ROC曲线探讨磷酸钠盐口服溶液致电解质紊乱的相关危险因素,并进行风险预测。方法:采用回顾性、观察性的研究方法收集使用磷酸钠盐口服溶液患者的病历资料,分析致电解质紊乱的危险因素,建立Logistic模型,绘制风险因素的ROC曲线。结果:共纳入294例(男183例,女111例)患者,78例(占26.5%)患者出现电解质紊乱,其中低钾血症有34例(占11.6%),高氯血症有29例(占9.9%),低钾高氯血症有7例(占2.4%),低钠血症有4例(占1.4%),低钠低氯血症有3例(占1.0%),低钠低氯低钾血症有1例(占0.34%)。单因素方差分析显示年龄、SCr、Ccr 3项指标的差异具有显著性,进一步多因素Logistic模型分析显示CCr分级是发生电解质紊乱的独立危险因素。根据Logistic模型分析结果,用CCr分级构建ROC曲线,曲线下面积0.816。CCr< 60 mL·min-1时,患者更易发生电解质紊乱,提示CCr是发生电解质紊乱的危险因素。结论:临床医师可根据患者CCr情况选择合适的肠道清洁药物。 相似文献
9.
The metastasis of cervical cancer has always been a clinical challenge. We investigated the effects of low-dose naltrexone (LDN) on the epithelial mesenchymal transition of cervical cancer cells in vitro as well as its influence on macrophage polarization and associated cytokines in vivo. The results suggested that LDN supressed the proliferation, migration and invasion abilities and promote their apoptosis in Hela cells, whereas the opioid growth factor receptor (OGFr) silenced significantly reversed these effects in vitro. Knockdown the expression of OGFr, the inhibitory of LDN on EMT was weakened. LDN could inhibit cervical cancer progression in nude mice. In additon, LDN indirectly reduced the number of tumor-associated macrophages (TAMs), mainly M2 macrophages, and decreased expression of anti-inflammatory factor IL-10 in the serum of nude mice. These findings demonstrate that LDN could be a potential treatment for cervical cancer. 相似文献
10.
BackgroundAs an ongoing worldwide health issue, Coronavirus disease 2019 (COVID–19) has been causing serious complications, including pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure. However, there is no decisive treatment approach available for this disorder, which is primarily attributed to the large amount of inflammatory cytokine production. We aimed to identify the effects of Nano-curcumin on the modulation of inflammatory cytokines in COVID-19 patients.MethodForty COVID-19 patients and 40 healthy controls were recruited and evaluated for inflammatory cytokine expression and secretion. Subsequently, COVID-19 patients were divided into two groups: 20 patients receiving Nano-curcumin and 20 patients as the placebo group. The mRNA expression and cytokine secretion levels of IL-1β, IL-6, TNF-α and IL‐18 were assessed by Real‐time PCR and ELISA, respectively.ResultOur primary results indicated that the mRNA expression and cytokine secretion of IL-1β, IL-6, TNF-α, and IL-18 were increased significantly in COVID-19 patients compared with healthy control group. After treatment with Nano-curcumin, a significant decrease in IL-6 expression and secretion in serum and in supernatant (P = 0.0003, 0.0038, and 0.0001, respectively) and IL-1β gene expression and secretion level in serum and supernatant (P = 0.0017, 0.0082, and 0.0041, respectively) was observed. However, IL-18 mRNA expression and TNF-α concentration were not influenced by Nano-curcumin.ConclusionNano-curcumin, as an anti-inflammatory herbal based agent, may be able to modulate the increased rate of inflammatory cytokines especially IL-1β and IL-6 mRNA expression and cytokine secretion in COVID-19 patients, which may cause an improvement in clinical manifestation and overall recovery. 相似文献