全文获取类型
收费全文 | 947篇 |
免费 | 66篇 |
国内免费 | 8篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 25篇 |
妇产科学 | 20篇 |
基础医学 | 152篇 |
口腔科学 | 1篇 |
临床医学 | 137篇 |
内科学 | 209篇 |
皮肤病学 | 9篇 |
神经病学 | 112篇 |
特种医学 | 29篇 |
外科学 | 78篇 |
综合类 | 1篇 |
预防医学 | 50篇 |
眼科学 | 5篇 |
药学 | 96篇 |
中国医学 | 1篇 |
肿瘤学 | 93篇 |
出版年
2023年 | 22篇 |
2022年 | 31篇 |
2021年 | 71篇 |
2020年 | 34篇 |
2019年 | 47篇 |
2018年 | 45篇 |
2017年 | 22篇 |
2016年 | 44篇 |
2015年 | 44篇 |
2014年 | 58篇 |
2013年 | 58篇 |
2012年 | 80篇 |
2011年 | 89篇 |
2010年 | 46篇 |
2009年 | 40篇 |
2008年 | 44篇 |
2007年 | 41篇 |
2006年 | 48篇 |
2005年 | 35篇 |
2004年 | 30篇 |
2003年 | 31篇 |
2002年 | 29篇 |
2001年 | 5篇 |
2000年 | 2篇 |
1999年 | 5篇 |
1998年 | 2篇 |
1995年 | 1篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 3篇 |
1988年 | 2篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1973年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有1021条查询结果,搜索用时 15 毫秒
61.
62.
63.
With the advancement of biotechnology in the last two decades, optimized and novel modalities and platforms of biologic moieties have emerged rapidly in drug discovery pipelines. In addition, new technologies for delivering therapeutic biologics (e.g., needle-free devices, nanoparticle complexes), as well as novel approaches for disease treatments (e.g., stem cell therapy, individualized medicine), continue to be developed. While pharmacokinetic studies are routinely carried out for therapeutic biologics, experiments that elucidate underlying mechanisms for clearance and biodistribution or identify key factors that govern absorption, distribution, metabolism, and excretion (ADME) of biologics often are not thoroughly conducted. Realizing the importance of biologics as therapeutic agents, pharmaceutical industry has recently begun to move the research focus from small molecules only to a blended portfolio consisting of both small molecules and biologics. This trend brings many opportunities for scientists working in the drug disposition research field. In anticipation of these opportunities and associated challenges, this review highlights impact of ADME studies on clinical and commercial success of biologics, with a particular focus on emerging applications and technologies and linkage with mechanistic pharmacokinetic/pharmacodynamic modeling and biomarker research. 相似文献
64.
Yulia Popova Palvannan Thayumanavan Elena Lonati Margarida Agroch?o Johan M. Thevelein 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(7):2890-2895
A novel concept in eukaryotic signal transduction is the use of nutrient transporters and closely related proteins as nutrient sensors. The action mechanism of these “transceptors” is unclear. The Pho84 phosphate transceptor in yeast transports phosphate and mediates rapid phosphate activation of the protein kinase A (PKA) pathway during growth induction. We have now identified several phosphate-containing compounds that act as nontransported signaling agonists of Pho84. This indicates that signaling does not require complete transport of the substrate. For the nontransported agonist glycerol-3-phosphate (Gly3P), we show that it is transported by two other carriers, Git1 and Pho91, without triggering signaling. Gly3P is a competitive inhibitor of transport through Pho84, indicating direct interaction with its phosphate-binding site. We also identified phosphonoacetic acid as a competitive inhibitor of transport without agonist function for signaling. This indicates that binding of a compound into the phosphate-binding site of Pho84 is not enough to trigger signaling. Apparently, signaling requires a specific conformational change that may be part of, but does not require, the complete transport cycle. Using Substituted Cysteine Accessibility Method (SCAM) we identified Phe160 in TMD IV and Val392 in TMD VIII as residues exposed with their side chain into the phosphate-binding site of Pho84. Inhibition of both transport and signaling by covalent modification of Pho84F160C or Pho84V392C showed that the same binding site is used for transport of phosphate and for signaling with both phosphate and Gly3P. Our results provide to the best of our knowledge the first insight into the molecular mechanism of a phosphate transceptor. 相似文献
65.
Dov Tiosano Yitzchak Schwartz Yulia Braver Amir Hadash Vardit Gepstein Yosef Weisman Avraham Lorber 《Journal of bone and mineral research》2011,26(9):2252-2260
Vitamin D deficiency has been linked to hypertension and an increased prevalence of cardiovascular risk factors and disease. Studies in vitamin D receptor knockout (VDR KO) mice revealed an overstimulated renin‐angiotensin system (RAS) and consequent high blood pressure and cardiac hypertrophy. VDR KO mice correspond phenotypically and metabolically to humans with hereditary 1,25‐dihydroxyvitamin D–resistant rickets (HVDRR). There are no data on the cardiovascular system in human HVDRR. To better understand the effects of vitamin D on the human cardiovascular system, the RAS, blood pressure levels, and cardiac structures were examined in HVDRR patients. Seventeen patients (9 males, 8 females, aged 6 to 36 years) with hereditary HVDRR were enrolled. The control group included age‐ and gender‐matched healthy subjects. Serum calcium, phosphorous, creatinine, 25‐hydroxyvitamin D [25(OH)D],1,25‐dihydroxyvitamin D3 [1,25(OH)2D3], parathyroid hormone (PTH), plasma rennin activity (PRA), aldosterone, angiotensin II (AT‐II), and angiotensin‐converting enzyme (ACE) levels were determined. Ambulatory 24‐hour blood pressure measurements and echocardiographic examinations were performed. Serum calcium, phosphorus, and alkaline phosphatase values were normal. Serum 1,25(OH)2D3 and PTH but not PRA and ACE levels were elevated in the HVDRR patients. AT‐II levels were higher than normal in the HVDRR patients but not significantly different from those of the controls. Aldosterone levels were normal in all HVDRR patients. No HVDRR patient had hypertension or echocardiographic pathology. These findings reveal that 6‐ to 36‐year‐old humans with HVDRR have normal renin and ACE activity, mild but nonsignificant elevation of AT‐II, normal aldosterone levels, and no hypertension or gross heart abnormalities. © 2011 American Society for Bone and Mineral Research 相似文献
66.
The authors review two cases of small bowel tumor. The first patient was operated electively with small bowel carcinoid causing multiplex liver metastases. The second patient was admitted because of massive gastrointestinal bleeding. After some diagnostic procedures bleeding of the small intestine was diagnosed. Urgent operation was performed and a bleeding jejunal tumor was removed. Gastrointestinal stroma cell tumor of the small bowel was found at histology. In connection with the patients some points about malignant small intestine tumors are analysed based on literature. 相似文献
67.
Balyasnikova IV Sun ZL Franke FE Berestetskaya YV Chubb AJ Albrecht RF Sturrock ED Danilov SM 《Hybridoma (2005)》2005,24(1):14-26
Angiotensin-converting enzyme (ACE) is a membrane-anchored ectoprotein that is proteolytically cleaved, yielding an enzymatically active soluble ACE. Two mouse monoclonal antibodies, MAbs 1B3 and 5C8, were generated to the C-terminal part of human soluble ACE. MAb 1B3 recognized the catalytically active ACE, as revealed by ELISA and precipitation assays, whereas Western blotting and immunohistochemisty on paraffin- embedded sections using MAb 5C8 detected denatured ACE. MAb 1B3 showed extensive cross-reactivity, recognizing 15 species out of the 16 tested. The binding of this MAb to ACE was greatly affected by conformational changes induced by adsorption on plastic, formalin fixation, and underglycosylation. Furthermore, MAb 1B3 binding to the mutated ACE (Pro1199Leu substitution in the juxtamembrane region, leading to a fivefold increase in serum ACE level) was markedly decreased. MAb 5C8 detected all the known expression sites of full-size ACE using formalin-fixed and paraffin-embedded human tissues. The sequential epitope for MAb 5C8 is formed by the last 11 amino acid residues of soluble ACE (Pro1193-Arg1203), whereas the conformational epitope for 1B3 is formed by a motif within these 11 amino acid residues and, in addition, by at least one stretch that includes Ala837-His839 located distal to the sequential epitope. Our findings demonstrated that MAbs 1B3 and 5C8 are very useful for the study of ACE shedding, for identification of mutations in stalk regions, and for studying alternatively spliced variants of ACE. In addition, binding of MAb 1B3 is a sensitive determinant of the integrity of soluble ACE. 相似文献
68.
69.
Daniely M Rona R Kaplan T Olsfanger S Elboim L Zilberstien Y Friberger A Kidron D Kaplan E Lew S Leibovitch I 《Urology》2005,66(6):1354-1359
70.