全文获取类型
| 收费全文 | 554篇 |
| 免费 | 18篇 |
| 国内免费 | 4篇 |
专业分类
| 耳鼻咽喉 | 8篇 |
| 儿科学 | 11篇 |
| 妇产科学 | 28篇 |
| 基础医学 | 47篇 |
| 口腔科学 | 14篇 |
| 临床医学 | 55篇 |
| 内科学 | 92篇 |
| 皮肤病学 | 8篇 |
| 神经病学 | 28篇 |
| 特种医学 | 12篇 |
| 外科学 | 70篇 |
| 综合类 | 16篇 |
| 一般理论 | 1篇 |
| 预防医学 | 73篇 |
| 眼科学 | 5篇 |
| 药学 | 70篇 |
| 中国医学 | 5篇 |
| 肿瘤学 | 33篇 |
出版年
| 2023年 | 11篇 |
| 2022年 | 13篇 |
| 2021年 | 21篇 |
| 2020年 | 23篇 |
| 2019年 | 18篇 |
| 2018年 | 20篇 |
| 2017年 | 20篇 |
| 2016年 | 19篇 |
| 2015年 | 21篇 |
| 2014年 | 20篇 |
| 2013年 | 26篇 |
| 2012年 | 43篇 |
| 2011年 | 33篇 |
| 2010年 | 17篇 |
| 2009年 | 16篇 |
| 2008年 | 17篇 |
| 2007年 | 18篇 |
| 2006年 | 18篇 |
| 2005年 | 22篇 |
| 2004年 | 16篇 |
| 2003年 | 14篇 |
| 2002年 | 16篇 |
| 2001年 | 8篇 |
| 2000年 | 10篇 |
| 1999年 | 8篇 |
| 1998年 | 2篇 |
| 1997年 | 2篇 |
| 1995年 | 2篇 |
| 1994年 | 2篇 |
| 1993年 | 3篇 |
| 1992年 | 2篇 |
| 1991年 | 5篇 |
| 1990年 | 7篇 |
| 1989年 | 5篇 |
| 1988年 | 4篇 |
| 1986年 | 7篇 |
| 1985年 | 2篇 |
| 1984年 | 3篇 |
| 1979年 | 7篇 |
| 1977年 | 5篇 |
| 1976年 | 3篇 |
| 1975年 | 6篇 |
| 1974年 | 4篇 |
| 1973年 | 3篇 |
| 1972年 | 3篇 |
| 1970年 | 5篇 |
| 1969年 | 4篇 |
| 1967年 | 4篇 |
| 1966年 | 6篇 |
| 1965年 | 2篇 |
排序方式： 共有576条查询结果，搜索用时 15 毫秒
561.
Generation and immunohistological characterization of human monoclonal antibodies to mammary carcinoma cells 总被引：3，自引：0，他引：3
The purpose of this study was to identify human antibodies generated against autologous breast tumor cells by the host's immune response. Accordingly, lymphocytes from lymph nodes of seven different patients with metastatic breast carcinomas were immortalized by fusing them with a nonsecreting variant of murine myeloma cells. The screening for binding of antibodies to tumor cells was performed by indirect immunoperoxidase staining of paraffin-embedded tissue sections of the autologous tumor. The selected hybrid cells, after being cloned three times, were stable for the secretion of immunoglobulins for over 2 years. A total of 81 human immunoglobulin-producing clones was obtained from an initial 595 wells with hybrid growth. Nine of these clones produced immunoglobulin M, none of which showed detectable binding to tissue antigens in breast. Seventy-two clones produced immunoglobulin G monoclonal antibodies, and 15 of these showed preferential binding to breast carcinoma cells. Three of these immunoglobulin G monoclonal antibodies were subjected to detailed immunohistological evaluations. Using these antibodies at concentrations ranging from 10 to 100 ng/tissue section, the morphologically normal mammary epithelial cells could be discriminated from their malignant counterparts. The antibodies showed diffuse staining of cytoplasmic components in the malignant counterparts. Under these conditions, lymphocytes, erythrocytes, and stromal cells in breast tissues were unstained. The antibodies showed variable reactivity with malignant epithelial cells of colon and stomach, and with normal epithelial cells lining the renal tubules and sebaceous glands in skin. Antigenic heterogeneity of malignant mammary epithelial cells was revealed. The antibodies may have value in the characterization of tumor-associated antigens responsible for inducing autologous immune responses. 相似文献
562.
A tumour-associated antigen (TAA.62) with an apparent mol. wt. of 62 kd, identified by a human monoclonal antibody (IgG2, kappa-light chain), was found to be expressed at elevated levels in the cytoplasmic compartment of malignant as compared with normal mammary epithelial cells in both tissues and cultured cells. Increased levels of cytoplasmic expression of the antigen were also observed in malignant cells of cervix, colon, kidney, lung, and stomach. The patterns of expression of TAA.62 in cultured cells mirrored those of tissues and the antigen was expressed at elevated levels in the established breast cancer lines or oncogenically transformed mammary carcinoma cell line (tumourigenic) compared with the immortalised mammary epithelial cell line (non-tumourigenic). Aliquots of TAA.62 were purified to homogeneity from the conditioned-medium of malignant and immortalised breast cells by immunoaffinity chromatography using immobilised anti-TAA.62 antibody, and gel filtration. Both preparations of TAA.62 yielded a single band with an apparent molecular weight of 62 kd under reducing condition on sodium dodecyl sulphate-polyacrylamide gel electrophoresis, and both were identical in terms of size and immunoreactivity to anti-TAA.62 antibody. However, TAA.62(T) isolated from tumourigenic cell lines itself interacted with a cell surface molecule having an apparent molecular weight of 160 kd on both the malignant and immortalised cells: TAA.62(I) isolated from immortalized cell lines, showed no comparable interaction. Scatchard analysis of the concentration-dependent binding of TAA.62(T) to 160 kd-receptor molecule revealed a 2.6 x 10(4) binding sites per cell. The association constant of such binding was determined to be approximately 16.6 nM. Finally, addition of anti-TAA.62 antibody to culture medium resulted in the inhibition of proliferation of the malignant cells, but showed no effect on the normal cells. The results suggest that TAA.62 may interact as a ligand with its 160 kd cell surface receptor with a possible growth related function. 相似文献
563.
564.
Abeer Sabry Safan Yahia Imam Naveed Akhtar Haya Al&#x;Taweel Ayman Zakaria Aiman Quateen Ahmed Own Saadat Kamran 《Clinical Case Reports》2022,10(6)
Atraumatic convexity subarachnoid hemorrhage (cSAH) is a rare non‐aneurysmal SAH, commonly due to ipsilateral internal carotid artery (ICA) stenosis. It is unusual for the cSAH to occur contralaterally to the infarct. We report two cases of acute ischemic stroke associated with contralateral and ipsilateral cSAH that had different presentations. 相似文献
565.
Virginia VanDelinder Ian Sickafoose Zachary I. Imam Randy Ko George D. Bachand 《RSC advances》2020,10(70):42810
The gliding motility of microtubule filaments has been used to study the biophysical properties of kinesin motors, as well as being used in a variety of nanotechnological applications. While microtubules are generally stabilized in vitro with paclitaxel (Taxol®), osmolytes such as polyethylene glycol (PEG) and trimethylamine N-oxide (TMAO) are also able to inhibit depolymerization over extended periods of time. High concentrations of TMAO have also been reported to reversibly inhibit kinesin motility of paclitaxel-stabilized microtubules. Here, we examined the effects of the osmolytes PEG, TMAO, and glycerol on stabilizing microtubules during gliding motility on kinesin-coated substrates. As previously observed, microtubule depolymerization was inhibited in a concentration dependent manner by the addition of the different osmolytes. Kinesin-driven motility also exhibited concentration dependent effects with the addition of the osmolytes, specifically reducing the velocity, increasing rates of pinning, and altering trajectories of the microtubules. These data suggest that there is a delicate balance between the ability of osmolytes to stabilize microtubules without inhibiting motility. Overall, these findings provide a more comprehensive understanding of how osmolytes affect the dynamics of microtubules and kinesin motors, and their interactions in crowded environments.Kinesin-driven motility was shown to be adversely affected in a concentration dependent manner by the addition of osmolytes: glycerol, polyethylene glycol, and trimethylamine N-oxide. 相似文献
566.
Muhammad Ikhlas Abdjan Nanik Siti Aminah Imam Siswanto Tin Myo Thant Alfinda Novi Kristanti Yoshiaki Takaya 《RSC advances》2020,10(70):42733
A combination of computational techniques has been carried out to predict the binding of nordentatin derivatives based on pyranocoumarin semi-synthesis with the target protein from the expression of the PDE4B gene. The inhibition of the cAMP pathway is the main target of anti-cancer drugs, which is responsible for uncontrolled cell division in cancer. Modeling was done using a combination of semi-empirical methods and the density functional theory (PM3-DFT/6-31G*/B3LYP) to obtain the optimal structure of a small ligand that could be modeled. Studies on the interaction of the ligands and amino acid residues on protein targets were carried out using a combination of molecular docking and molecular dynamic simulation. Molecular docking based on functional grid scores showed a very good native ligand pose with an RMSD of 0.93 Å in determining the initial coordinates of the ligand–receptor interactions. Furthermore, the amino acid residues responsible for interaction through H-bonds were Tyr103, His104, His177, Met217, and Gln313. The binding free energy (kcal mol−1) results of the candidates were PS-1 (−36.84 ± 0.31), PS-2 (−35.34 ± 0.28), PS-3 (−26.65 ± 0.30), PS-5 (−42.66 ± 0.26), PS-7 (−35.33 ± 0.23), and PS-9 (−32.57 ± 0.20), which are smaller than that of the native ligand Z72 (−24.20 ± 0.19), and thus these have good potential as drugs that can inhibit the cAMP pathway. These results provide theoretical information for the efficient inhibition of the cAMP pathway in the future.A combination of computational techniques has been carried out to predict the binding of nordentatin derivatives based on pyranocoumarin semi-synthesis with the target protein from the expression of the PDE4B gene. 相似文献
567.
Ashraf Imam Keren Tzukert Hadar Merhav Riham Imam Samir Abu-Gazala Roy Abel Michal Dranitzki Elhalel Abed Khalaileh 《World Journal of Transplantation》2020,10(9):223-229
Kidney transplantation at the time of a global viral pandemic has become challenging in many aspects. Firstly, we must reassess deceased donor safety (for the recipient) especially in communities with a relatively high incidence of coronavirus disease 19 (COVID-19). With respect to elective live donors, if one decides to do them at all, similar considerations must be made that may impose undue hardship on the donor. Recipient selection is also problematic since there is clear evidence of a much higher morbidity and mortality from COVID-19 for patients older than 60 and those with comorbidities such as hypertension, diabetes, obesity and lung disease. Unfortunately, many, if not most of dialysis patients fit that mold. We may and indeed must reassess our allocation policies, but this must be done based on data rather than conjecture. Follow-up routines must be re-engineered to minimize patient travel and exposure. Reliance on technology and telemedicine is paramount. Making this technology available to patients is extremely important. Modifying or changing immunosuppression protocols is controversial and not based on clinical studies. Nevertheless, we should reassess the need for induction therapy across the board for ordinary patients and the more liberal use of mammalian target of rapamycin inhibitors in transplant patients with proven infection. 相似文献
568.
569.
570.
Muhammad Ikhlas Abdjan Nanik Siti Aminah Alfinda Novi Kristanti Imam Siswanto Baso Ilham Andika Pramudya Wardana Yoshiaki Takaya 《RSC advances》2023,13(6):3438
α-glucosidase is an enzyme that catalyzes the release of α-glucose molecules through hydrolysis reactions. Regulation of this enzyme can increase sugar levels in type-2 diabetes mellitus (DM) patients. Pyranocoumarin derivatives have been identified as α-glucosidase inhibitors. Through an in silico approach, this work studied the inhibition of three pyranocoumarin compounds against the α-glucosidase at the molecular level. Molecular docking and molecular dynamics simulation were performed to understand the dynamics behavior of pyranocoumarin derivatives against α-glucosidase. The prediction of free binding energy (ΔGbind) using the Quantum Mechanics/Molecular Mechanics-Generalized Born (QM/MM-GBSA) approach for each system had the following results, PC1-α-Glu: −13.97 kcal mol−1, PC2-α-Glu: −3.69 kcal mol−1, and PC3-α-Glu: −13.68 kcal mol−1. The interaction energy of each system shows that the grid score, ΔGbind, and ΔGexp values had a similar correlation, that was PC1-α-Glu > PC3-α-Glu > PC2-α-Glu. Additionally, the decomposition energy analysis (ΔGresiduebind) was carried out to find out the contribution of the key binding residue. The results showed that there were 15 key binding residues responsible for stabilizing pyranocumarin binding with criteria of ΔGresiduebind < −1.00 kcal mol−1. The evaluation presented in this work could provide information on the molecular level about the inhibitory efficiency of pyranocoumarin derivatives against a-glucosidase enzyme based on computational studies.We presented the structure-based approach (molecular docking and MD simulation) to understand the dynamics behavior and inhibitory efficiency of pyranocoumarin derivatives against α-glucosidase at the molecular level. 相似文献