全文获取类型
收费全文 | 5663篇 |
免费 | 279篇 |
国内免费 | 235篇 |
专业分类
耳鼻咽喉 | 8篇 |
儿科学 | 132篇 |
妇产科学 | 28篇 |
基础医学 | 645篇 |
口腔科学 | 44篇 |
临床医学 | 224篇 |
内科学 | 580篇 |
皮肤病学 | 35篇 |
神经病学 | 1110篇 |
特种医学 | 108篇 |
外科学 | 185篇 |
综合类 | 628篇 |
预防医学 | 653篇 |
眼科学 | 68篇 |
药学 | 1276篇 |
中国医学 | 354篇 |
肿瘤学 | 99篇 |
出版年
2023年 | 52篇 |
2022年 | 134篇 |
2021年 | 179篇 |
2020年 | 104篇 |
2019年 | 93篇 |
2018年 | 94篇 |
2017年 | 98篇 |
2016年 | 120篇 |
2015年 | 150篇 |
2014年 | 184篇 |
2013年 | 272篇 |
2012年 | 230篇 |
2011年 | 242篇 |
2010年 | 186篇 |
2009年 | 159篇 |
2008年 | 198篇 |
2007年 | 209篇 |
2006年 | 147篇 |
2005年 | 210篇 |
2004年 | 171篇 |
2003年 | 169篇 |
2002年 | 166篇 |
2001年 | 166篇 |
2000年 | 143篇 |
1999年 | 140篇 |
1998年 | 141篇 |
1997年 | 147篇 |
1996年 | 130篇 |
1995年 | 125篇 |
1994年 | 115篇 |
1993年 | 103篇 |
1992年 | 131篇 |
1991年 | 118篇 |
1990年 | 132篇 |
1989年 | 111篇 |
1988年 | 91篇 |
1987年 | 71篇 |
1986年 | 82篇 |
1985年 | 106篇 |
1984年 | 93篇 |
1983年 | 79篇 |
1982年 | 80篇 |
1981年 | 63篇 |
1980年 | 54篇 |
1979年 | 40篇 |
1978年 | 33篇 |
1977年 | 26篇 |
1976年 | 24篇 |
1974年 | 14篇 |
1973年 | 17篇 |
排序方式: 共有6177条查询结果,搜索用时 15 毫秒
1.
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
2.
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
3.
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
4.
5.
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
6.
S. Vemuri 《Chemical biology & drug design》2005,65(4):433-439
Abstract: Precise determination of the peptide content in drug substance samples depends highly upon the particular peptide compound and methodology used. Four independent methods were evaluated and compared to determine which would produce the best experimental precision for analysis of thymalfasin (thymosin α‐1). Four different methods were evaluated including elemental analysis (CHN), quantitative amino acid analysis (AAA), high‐performance liquid chromatography (HPLC), and Kjeldahl. This study demonstrates that the AAA method is highly variable in one laboratory while quite precise in another laboratory. Similarly, HPLC results depended on the laboratory conducting the study with more precise values obtained under cGMP. On the contrary, the CHN method yielded highly precise [i.e. <2% coefficient of variation (CV)] values. As precise knowledge of protein content is fundamental for the compounding of final pharmaceutical product of a specific potency, the CHN analysis is recommended for peptide content determination of the drug substance thymalfasin. 相似文献
7.
市售三厂家18种复方氨基酸注射液的质量评价 总被引:3,自引:0,他引:3
目的对市售3厂家(A、B和E)共9批18种复方氨基酸注射液进行质量比较。方法参考国内外同类产品质量标准,从澄明度、透光率、性状、pH值、不溶性微粒、抗氧剂量、细菌内毒素和含量等方面进行比较。结果外观均为无色澄明液体,430nm波长处透光率均大于99%,pH在5.42~6.61间;A、B、E3厂不溶性微粒≥10、≥25μm的粒子数分别为1.41、0.32,0.83、0.21和1.55、0.56个/ml;抗氧剂的量分别为<33、近330和>500mg/L;细菌内毒素检查与含量测定符合中国药典及国家标准要求。结论不同厂家的产品质量确实存在一定的差异。 相似文献
8.
W A Turski M Dziki E Urbanska L S Calderazzo-Filho E A Cavalheiro 《Synapse (New York, N.Y.)》1991,7(3):173-180
Systemic (s.c.) administration of aminooxyacetic acid (AOAA) in mice triggered clonic convulsions with a CD50 (convulsive dose) of 68 mg/kg (range 54-86). AOAA also induced clonic convulsions in mice subjected to intracerebroventricular administration of the drug with a CD50 of 0.04 mumols (range 0.028-0.06). At the onset of convulsions induced by systemic AOAA (CD97;150 mg/kg), the GAD activity in the frontal cortex and hippocampus was not affected. GABA mimetic drugs, progabide and gabaculine, had no effect on convulsions induced by AOAA. Convulsions induced by systemic administration of AOAA were blocked by diazepam, phenobarbital, and valproate. Ethosuximide, trimethadione, acetazolamide, diphenylhydantoin, and carbamazepine remained ineffective. L-Phenylisopropyladenosine was also found to protect mice against AOAA-induced convulsions, whereas atropine and baclofen had no effect. The seizures induced by intracerebroventricular administration of AOAA (CD97; 0.1 mumols) were blocked by coadministration of preferential N-methyl-D-aspartate antagonists, D-(-)-2-aminophosphonoheptanoic (AP7), 3-[+/-)-2-carboxypiperazine-4-yl)-propyl-1-phosphonic (CPP), and kynurenic acid (KYNA); preferential quisqualate/kainate antagonists, 6-cyano-7-nitro-quinoxaline-2,3-dione and gamma-D-glutamylaminomethylsulphonic acid, remained inactive in the range of dosages sufficient to block seizures induced by quisqualic acid or kainic acid. The antagonistic action of antiepileptic drugs effective against seizures induced by excitatory amino acids (diazepam and valproate), and drugs acting on excitatory amino acid receptors (AP7, CPP, and KYNA) upon seizures induced by AOAA suggests an involvement of excitatory neurotransmission in the convulsant action of the drug. 相似文献
9.
保守氨基酸残基在生物进化过程中具有较强的稳定性,一般不会发生太大的变化;生物信息学认为:氨基酸序列决定蛋白质结构,蛋白质结构决定蛋白质功能。因此,作者基于氨基酸的生化特性、几何特性和动态特性描述了一个新颖的算法去发现蛋白酶家族中的保守氨基酸残基,而保守氨基酸残基将对蛋白质的结构和功能的研究具有重要的意义。 相似文献
10.