全文获取类型
收费全文 | 14098篇 |
免费 | 713篇 |
国内免费 | 589篇 |
专业分类
耳鼻咽喉 | 20篇 |
儿科学 | 473篇 |
妇产科学 | 143篇 |
基础医学 | 1493篇 |
口腔科学 | 125篇 |
临床医学 | 838篇 |
内科学 | 2238篇 |
皮肤病学 | 129篇 |
神经病学 | 1506篇 |
特种医学 | 242篇 |
外科学 | 578篇 |
综合类 | 1317篇 |
现状与发展 | 4篇 |
预防医学 | 2265篇 |
眼科学 | 121篇 |
药学 | 2711篇 |
中国医学 | 867篇 |
肿瘤学 | 330篇 |
出版年
2023年 | 169篇 |
2022年 | 457篇 |
2021年 | 585篇 |
2020年 | 406篇 |
2019年 | 357篇 |
2018年 | 314篇 |
2017年 | 334篇 |
2016年 | 379篇 |
2015年 | 392篇 |
2014年 | 640篇 |
2013年 | 934篇 |
2012年 | 541篇 |
2011年 | 686篇 |
2010年 | 503篇 |
2009年 | 477篇 |
2008年 | 524篇 |
2007年 | 506篇 |
2006年 | 432篇 |
2005年 | 496篇 |
2004年 | 422篇 |
2003年 | 366篇 |
2002年 | 366篇 |
2001年 | 326篇 |
2000年 | 304篇 |
1999年 | 277篇 |
1998年 | 280篇 |
1997年 | 273篇 |
1996年 | 241篇 |
1995年 | 221篇 |
1994年 | 221篇 |
1993年 | 207篇 |
1992年 | 210篇 |
1991年 | 198篇 |
1990年 | 208篇 |
1989年 | 210篇 |
1988年 | 182篇 |
1987年 | 145篇 |
1986年 | 149篇 |
1985年 | 197篇 |
1984年 | 179篇 |
1983年 | 138篇 |
1982年 | 156篇 |
1981年 | 125篇 |
1980年 | 120篇 |
1979年 | 95篇 |
1978年 | 86篇 |
1977年 | 73篇 |
1976年 | 66篇 |
1974年 | 41篇 |
1973年 | 49篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
Gut bacteria and gut barrier plays important roles in body homeostasis. Ciprofloxacin (CPFX) is widely used to treat bacterial infections. However, whether high dosage of CPFX has side effects on gut barrier integrity is still unclear. Our results indicated that the High CPFX treatment (1 mg/ml) caused weight loss, nervousness, anorexia, and increased apoptosis cells in gut, but less influence was observed in the Low CPFX group (0.2 mg/ml). Meanwhile, the High CPFX treatment impaired tight junction molecules Ocln/ZO-1 level and down-regulated antibacterial genes expression (reg3γ, pla2g2α and defb1). Further, the High CPFX treatment increased pro-inflammatory cytokine IL-1β in intestinal tract, decreased IL-17A of duodenum but increased IL-17A of colon at day 37. In addition, the gut bacterial diversity and richness behaved significantly loss regarding CPFX treatment, especially in the High CPFX group during the experiment. Indole exhibited sharply decline in both Low and High CPFX groups at day 7, and the High CPFX mice needed longer time on restoring indole level. Meanwhile, CPFX treatment strongly decreased the concentrations of butyric acid and valeric acid at day 1. Correlation analysis indicated that the linked patterns between the key bacteria (families Bacteroidales_S247, Ruminococcaceae and Desulfovibrionaceae) and metabolites (indole and butyric acid) were disturbed via the CPFX treatment. In conclusion, the High CPFX treatment impaired the gut barrier with the evidence of reduced expression of tight junction proteins, increased apoptosis cells and inflammatory cells, decreased the bacterial diversity and composition, which suggesting a proper antibiotic-dosage use should be carefully considered in disease treatment. 相似文献
2.
Lorena Martin-Morales Sara Manzano Maria Rodrigo-Faus Adrian Vicente-Barrueco Victor Lorca Gonzalo Núñez-Moreno Paloma Bragado Almudena Porras Trinidad Caldes Pilar Garre Alvaro Gutierrez-Uzquiza 《International journal of cancer. Journal international du cancer》2023,152(2):283-297
Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future. 相似文献
3.
Astrid Ruiz-Marg in Berenice M Rom n-Calleja Paulina Moreno-Guill n Jos A Gonz lez-Regueiro Deyanira K sulas-Delint Alejandro Campos-Murgu a Nayelli C Flores-Garc a Ricardo Ulises Mac as-Rodr guez 《World journal of gastrointestinal oncology》2021,13(10):1440-1452
Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and presents together with cirrhosis in most cases. In addition to commonly recognized risk factors for HCC development, such as hepatitis B virus/hepatitis C virus infection, age and alcohol/tobacco consumption, there are nutritional risk factors also related to HCC development including high intake of saturated fats derived from red meat, type of cooking (generation of heterocyclic amines) and contamination of foods with aflatoxins. On the contrary, protective nutritional factors include diets rich in fiber, fruits and vegetables, n-3 polyunsaturated fatty acids and coffee. While the patient is being evaluated for staging and treatment of HCC, special attention should be paid to nutritional support, including proper nutritional assessment and therapy by a multidisciplinary team. It must be considered that these patients usually develop HCC on top of long-lasting cirrhosis, and therefore they could present with severe malnutrition. Cirrhosis-related complications should be properly addressed and considered for nutritional care. In addition to traditional methods, functional testing, phase angle and computed tomography scan derived skeletal muscle index-L3 are among the most useful tools for nutritional assessment. Nutritional therapy should be centered on providing enough energy and protein to manage the increased requirements of both cirrhosis and cancer. Supplementation with branched-chain amino acids is also recommended as it improves response to treatment, nutritional status and survival, and finally physical exercise must be encouraged and adapted to individual needs. 相似文献
4.
5.
Mengdie Jiang Bihan Wu Yongbing Sun Yanhuai Ding Yixi Xie 《Toxicology mechanisms and methods》2019,29(4):291-299
In a biological microenvironment, free fatty acids (FFA) as ubiquitous biological molecules might interact with nanoparticles (NPs) and consequently change the toxicological responses. However, whether the chemical structures of FFA could influence their interactions with NPs remain unknown. This study investigated the interactions between ZnO NPs and saturated or unsaturated FFA (complexed to BSA), namely stearic acid (SA, C18:0), oleic acid (OA, C18:1), and α-linolenic acid (ALA, C18:3). It was shown that BSA, SA, OA, and ALA increased the atomic force microscope (AFM) heights as well the polydispersity index (PDI) of ZnO NPs. BSA modestly protected THP-1 macrophages from ZnO NP exposure, whereas OA and ALA led to relatively less cyto-protective effects of BSA. Moreover, only co-exposure to ZnO NPs and SA significantly promoted the release of interleukin-8. BSA, SA, OA, and ALA equally changed intracellular ROS and Zn ions associated with ZnO exposure, but co-exposure to ZnO NPs and OA/ALA particularly activated the expression of endoplasmic reticulum stress-apoptosis genes. In combination, these results showed that FFA could influence the colloidal aspects and toxicological signaling pathway of ZnO NPs, which is dependent on the number of unsaturated bonds of FFA. 相似文献
6.
The peri-implantation period of pregnancy is critical for conceptus development, implantation, and signaling for establishment of pregnancy. This study evaluated the effects of bisphenol A (BPA) on proliferation, adhesion, and migration of porcine trophectoderm (pTr2) cells, expression of transporters of arginine and synthesis of amino acids. All concentrations of BPA decreased proliferation and adhesion of pTr2 cells after 96 h compared to the control group. Lower concentrations of BPA (1 × 10−9, 1 × 10-8, 10-7M) increased (P < 0.05), but higher concentrations of BPA (1 × 10-5, 1 × 10-4 M) decreased migration of pTr2 cells. BPA increased expression of SLC7A1 mRNA at lower concentrations (1 × 10−9 to 1 × 10-6M) and SL7A6, another cationic acid transporter, at higher concentrations (1 × 10-5, 1 × 10-4 M). BPA also down-regulated the expression of IGF1 and IGF1 receptor at concentrations of 1 × 10-7 to 1 × 10-4 M compared to the control group. The expression of mRNAs for aquaporins (AQP) 3 and 4 were reduced at all concentrations of BPA, but at lower concentrations of BPA, (1 × 10−9 to 1 × 10-8M) expression of AQP9 mRNA increased and the expression of AQP11 was not affected by BPA (P > 0.05). There was an inhibitory effect of BPA on the release of synthesis of asparagine, threonine, taurine, tryptophan, and ornithine into the culture medium by pTr2 cells. Collectively, BPA adversely affected the expression of transporters for cationic amino acids like arginine, as well as AQPs, IGF1, and IGF1R associated with proliferation, migration, and adhesion of pTr2 cells. Those adverse effects would likely increase pregnancy losses during the peri-implantation period of pregnancy. 相似文献
7.
《Nutrition, metabolism, and cardiovascular diseases : NMCD》2022,32(12):2883-2889
Background and aimsCoronary artery disease (CAD) is the principal cause of death in individuals with non-alcoholic fatty liver disease (NAFLD). The aim of this study was to use genetic epidemiology to study the association between de novo lipogenesis (DNL), one of the major pathways leading to NAFLD, and CAD risk.Methods and resultsDNL susceptibility genes were used as instruments and selected using three approaches: 1) genes that are associated with both high serum triglycerides and low sex hormone-binding globulin, both downstream consequences of DNL (unbiased approach), 2) genes that have a known role in DNL (biased approach), and 3) genes that have been associated with serum fatty acids, used as a proxy of DNL. Gene-CAD effect estimates were retrieved from the meta-analysis of CARDIoGRAM and the UK Biobank (~76014 cases and ~264785 controls). Effect estimates were clustered using a fixed-effects meta-analysis. Twenty-two DNL susceptibility genes were identified by the unbiased approach, nine genes by the biased approach and seven genes were associated with plasma fatty acids. Clustering of genes selected in the unbiased and biased approach showed a statistically significant association with CAD (OR:1.016, 95%CI:1.012; 1.020 and OR:1.013, 95%CI:1.007; 1.020, respectively), while clustering of fatty acid genes did not (OR:1.004, 95%CI:0.996–1.011). Subsequent exclusion of potential influential outliers did reveal a statistically significant association (OR:1.009, 95%CI:1.000; 1.018).ConclusionsDNL susceptibility genes are associated with an increased risk of CAD. These findings suggest that DNL may be involved in the pathogenesis of CAD and favor further development of strategies that target NAFLD through DNL. 相似文献
8.
R GOKAL 《Nephrology (Carlton, Vic.)》1996,2(S1):s159-s162
Summary: Current peritoneal dialysis solutions are not biocompatible, particularly in respect to low pH, high osmolality and use of lactate. In addition, glucose is not an ideal osmotic agent. Recent advances in the formulation of peritoneal dialysis fluids aim to provide a more physiological environment to preserve membrane integrity. the effects of pH and lactate have been overcome by the use of bicarbonate based solutions whilst icodextrin (glucose polymers) often prolonged ultrafiltration in spite of being isomotic to uraemic plasma. Future formulations will see a combination of osmotic agents (including amino acids) and bicarbonate to achieve a more biocompatible solution whilst still meeting the ultrafiltration needs of the patients. Additives (glycosaminoglycans, procysteine) may protect the peritoneum from free radical injury. 相似文献
9.
10.
J.K. MOHANA RAO 《Chemical biology & drug design》1987,29(2):276-281
Based on residue characteristic physical parameters, a new scoring matrix, called EMPAR, for amino acid exchanges in proteins was obtained. When comparing protein sequences for detecting homologies, the use of this matrix in place of the Dayhoff log-odds matrix yields results that reflect the topological similarities in the proteins. The use of EMPAR is equivalent to the parametric correlation coefficient approach of Ooi and his colleagues. This matrix correlates at 0.63 with the Dayhoff matrix. 相似文献