全文获取类型
收费全文 | 206篇 |
免费 | 22篇 |
国内免费 | 1篇 |
专业分类
儿科学 | 17篇 |
妇产科学 | 1篇 |
基础医学 | 19篇 |
口腔科学 | 4篇 |
临床医学 | 23篇 |
内科学 | 42篇 |
皮肤病学 | 4篇 |
神经病学 | 8篇 |
特种医学 | 12篇 |
外科学 | 7篇 |
综合类 | 8篇 |
预防医学 | 10篇 |
眼科学 | 1篇 |
药学 | 36篇 |
肿瘤学 | 37篇 |
出版年
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 3篇 |
2020年 | 3篇 |
2019年 | 2篇 |
2018年 | 4篇 |
2017年 | 5篇 |
2016年 | 3篇 |
2015年 | 6篇 |
2014年 | 7篇 |
2013年 | 15篇 |
2012年 | 12篇 |
2011年 | 11篇 |
2010年 | 10篇 |
2009年 | 12篇 |
2008年 | 13篇 |
2007年 | 17篇 |
2006年 | 10篇 |
2005年 | 3篇 |
2004年 | 4篇 |
2003年 | 3篇 |
2002年 | 2篇 |
2001年 | 2篇 |
2000年 | 3篇 |
1999年 | 7篇 |
1998年 | 5篇 |
1997年 | 9篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1993年 | 6篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 4篇 |
1989年 | 5篇 |
1988年 | 7篇 |
1987年 | 5篇 |
1986年 | 3篇 |
1985年 | 4篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1975年 | 1篇 |
1966年 | 1篇 |
1954年 | 1篇 |
1952年 | 1篇 |
1940年 | 1篇 |
排序方式: 共有229条查询结果,搜索用时 15 毫秒
21.
Zhao XQ Xie JD Chen XG Sim HM Zhang X Liang YJ Singh S Talele TT Sun Y Ambudkar SV Chen ZS Fu LW 《Molecular pharmacology》2012,82(1):47-58
Neratinib, an irreversible inhibitor of epidermal growth factor receptor and human epidermal receptor 2, is in phase III clinical trials for patients with human epidermal receptor 2-positive, locally advanced or metastatic breast cancer. The objective of this study was to explore the ability of neratinib to reverse tumor multidrug resistance attributable to overexpression of ATP-binding cassette (ABC) transporters. Our results showed that neratinib remarkably enhanced the sensitivity of ABCB1-overexpressing cells to ABCB1 substrates. It is noteworthy that neratinib augmented the effect of chemotherapeutic agents in inhibiting the growth of ABCB1-overexpressing primary leukemia blasts and KBv200 cell xenografts in nude mice. Furthermore, neratinib increased doxorubicin accumulation in ABCB1-overexpressing cell lines and Rhodamine 123 accumulation in ABCB1-overexpressing cell lines and primary leukemia blasts. Neratinib stimulated the ATPase activity of ABCB1 at low concentrations but inhibited it at high concentrations. Likewise, neratinib inhibited the photolabeling of ABCB1 with [(125)I]iodoarylazidoprazosin in a concentration-dependent manner (IC(50) = 0.24 μM). Neither the expression of ABCB1 at the mRNA and protein levels nor the phosphorylation of Akt was affected by neratinib at reversal concentrations. Docking simulation results were consistent with the binding conformation of neratinib within the large cavity of the transmembrane region of ABCB1, which provides computational support for the cross-reactivity of tyrosine kinase inhibitors with human ABCB1. In conclusion, neratinib can reverse ABCB1-mediated multidrug resistance in vitro, ex vivo, and in vivo by inhibiting its transport function. 相似文献
22.
Reconstitution of a bacterial periplasmic permease in proteoliposomes and demonstration of ATP hydrolysis concomitant with transport. 总被引:25,自引:4,他引:21
下载免费PDF全文
![点击此处可从《Proceedings of the National Academy of Sciences of the United States of America》网站下载免费的PDF全文](/ch/ext_images/free.gif)
L Bishop R Agbayani Jr S V Ambudkar P C Maloney G F Ames 《Proceedings of the National Academy of Sciences of the United States of America》1989,86(18):6953-6957
The histidine periplasmic permease of Salmonella typhimurium has been partially purified and reconstituted into proteoliposomes. In this in vitro preparation, transport activity is completely dependent on the presence of all four permease proteins (HisJ, HisQ, HisM, and HisP) and on internal ATP. The reconstituted system shows initial rates of transport that are comparable to those obtained with right-side-out membrane vesicles and it establishes a 100-fold concentration gradient for histidine. Proteoliposomes also transport histidine when GTP replaces ATP. Proteoliposomes do not catalyze significant ATP hydrolysis until histidine transport is initiated by addition of substrate along with HisJ, the water-soluble histidine-binding protein. Both initially and throughout the course of substrate transport there is a concomitant hydrolysis of ATP, with an apparent stoichiometry (ATP/histidine) of 5:1. These experiments demonstrate directly that ATP is the source of energy for periplasmic permeases, thus resolving previous controversies on this topic. 相似文献
23.
24.
25.
Manisha Nada D Rohit SV Singh AK Khurana Sakshi Lochab Anjali Kharolia 《Indian journal of ophthalmology》2022,70(11):3854
Purpose:Incisions in cataract surgery can be modified in various ways in terms of size, shape, and axis to reduce or tailor astigmatism. This study was conducted to examine the effect of site (superior vs, temporal) and shape (frown vs. V-shaped, chevron) of scleral incisions for cataract surgery on corneal curvature.Methods:The prospective study was carried out on 200 consecutive patients with senile cataract and who were planned for surgery at a tertiary eye hospital in north India. The placement of the incision was decided by the steeper corneal meridian—whether superior or temporal—and then patients of these two groups were randomized for frown and V-shaped incision; in this way, four groups of 50 patients each were formed. Follow-up was done on day 1, at 2 weeks, 4 weeks, 8 weeks, and 12 weeks. At each follow-up, post-operative keratometry with routine postoperative examination was done. The results were statistically analyzed by using student’s t-test, Chi-squared test, and the Pearson correlation coefficient.Results:In all the four groups, the difference of preoperative astigmatism and surgically-induced astigmatism was statistically highly significant. The analysis of uncorrected visual acuity (UCVA) was statistically significant (P < 0.05) on postoperative day 1 and at 2, 4, and 12 postoperative weeks; it was statistically insignificant (P > 0.05) at postoperative week 8.Conclusion:Temporal incisions result in lesser postoperative surgically induced astigmatism (SIA) than superior incisions. Chevron incisions result in minimal change in corneal curvature. This effect can be utilized to tailor the postoperative astigmatism. 相似文献
26.
Lacroix-Desmazes S; Mouthon L; Pashov A; Barreau C; Kaveri SV; Kazatchkine MD 《International immunology》1997,9(8):1175-1183
By using a quantitative immunoblotting technique, we have analyzed the
repertoires of antibody reactivities of IgM directed toward self antigens
in the serum of patients with Waldenstrom's macroglobulinemia (WM) and in
the serum of healthy adults. Monoclonal IgM of patients with WM expressed
various degrees of polyreactivity and a high degree of heterogeneity with
regard to the number and the nature of the protein bands that were
recognized in homologous tissue extracts. Heterogeneous patterns of
reactivity of WM IgM contrasted with the conserved profiles of reactivity
of IgM in the serum of healthy blood donors. Protein bands that were
recognized by WM IgM belonged to the restricted set of self antigens
recognized in homologous tissues by normal polyclonal IgM, indicating the
absence of a disease-specific reactivity profile of monoclonal WM IgM.
Thus, monoclonal IgM that is present in large amounts in WM distorts the
homogeneous pattern of reactivity of natural antibodies with self antigens
which characterizes the natural antibody repertoire of healthy individuals.
相似文献
27.
Kuang YH Patel JP Sodani K Wu CP Liao LQ Patel A Tiwari AK Dai CL Chen X Fu LW Ambudkar SV Korlipara VL Chen ZS 《Biochemical pharmacology》2012,84(6):766-774
OSI-930, a dual c-Kit and KDR tyrosine kinase inhibitor, is reported to have undergone a Phase I dose escalation study in patients with advanced solid tumors. A series of fifteen pyridyl and phenyl analogues of OSI-930 were designed and synthesized. Extensive screening of these compounds led to the discovery that nitropyridyl and ortho-nitrophenyl analogues, VKJP1 and VKJP3, were effective in reversing ABC subfamily G member 2 (ABCG2) transporter-mediated multidrug resistance (MDR). VKJP1 and VKJP3 significantly sensitized ABCG2-expressing cells to established substrates of ABCG2 including mitoxantrone, SN-38, and doxorubicin in a concentration-dependent manner, but not to the non-ABCG2 substrate cisplatin. However, they were unable to reverse ABCB1- or ABCC1-mediated MDR indicating their selectivity for ABCG2. Western blotting analysis was performed to evaluate ABCG2 expression and it was found that neither VKJP1 nor VKJP3 significantly altered ABCG2 protein expression for up to 72h. [(3)H]-mitoxantrone accumulation study demonstrated that VKJP1 and VKJP3 increased the intracellular accumulation of [(3)H]-mitoxantrone, a substrate of ABCG2. VKJP1 and VKJP3 also remarkably inhibited the transport of [(3)H]-methotrexate by ABCG2 membrane vesicles. Importantly, both VKJP1 and VKJP3 were efficacious in stimulating the activity of ATPase of ABCG2 and inhibited the photoaffinity labeling of this transporter by its substrate [(125)I]-iodoarylazidoprazosin. The results suggested that VKJP1 and VKJP3, specifically inhibit the function of ABCG2 through direct interaction with its substrate binding site(s). Thus VKJP1 and VKJP3 represent a new class of drugs for reducing MDR in ABCG2 over-expressing tumors. 相似文献
28.
Ambudkar IS 《Handbook of experimental pharmacology》2007,(179):541-557
Transient receptor potential (TRP) channels are members of a relatively newly described family of cation channels that display a wide range of properties and mechanisms of activation. The exact physiological function and regulation of most of these channels have not yet been conclusively determined. Studies over the past decade have revealed important features of the channels that contribute to their function. These include homomeric interactions between TRP monomers, selective heteromeric interactions within members of the same subfamily, interactions of TRPs with accessory proteins and assembly into macromolecular signaling complexes, and regulation within functionally distinct cellular microdomains. Further, distinct constitutive and regulated vesicular trafficking mechanisms have a critical role not only in controlling the surface expression of TRP channels but also their activation in response to stimuli. A number of cellular components such as cytoskeletal and scaffolding proteins also contribute to TRP channel trafficking. Thus, mechanisms involved in the assembly and trafficking of TRP channels control their plasma membrane expression and critically impact their function and regulation. 相似文献
29.