全文获取类型
收费全文 | 1267篇 |
免费 | 93篇 |
国内免费 | 50篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 7篇 |
妇产科学 | 14篇 |
基础医学 | 144篇 |
口腔科学 | 7篇 |
临床医学 | 42篇 |
内科学 | 172篇 |
皮肤病学 | 8篇 |
神经病学 | 273篇 |
特种医学 | 18篇 |
外科学 | 37篇 |
综合类 | 56篇 |
预防医学 | 31篇 |
眼科学 | 16篇 |
药学 | 452篇 |
中国医学 | 37篇 |
肿瘤学 | 92篇 |
出版年
2024年 | 2篇 |
2023年 | 14篇 |
2022年 | 32篇 |
2021年 | 39篇 |
2020年 | 27篇 |
2019年 | 45篇 |
2018年 | 48篇 |
2017年 | 63篇 |
2016年 | 58篇 |
2015年 | 53篇 |
2014年 | 61篇 |
2013年 | 125篇 |
2012年 | 70篇 |
2011年 | 76篇 |
2010年 | 63篇 |
2009年 | 95篇 |
2008年 | 84篇 |
2007年 | 65篇 |
2006年 | 71篇 |
2005年 | 101篇 |
2004年 | 64篇 |
2003年 | 42篇 |
2002年 | 22篇 |
2001年 | 17篇 |
2000年 | 14篇 |
1999年 | 12篇 |
1998年 | 6篇 |
1997年 | 17篇 |
1996年 | 3篇 |
1995年 | 4篇 |
1994年 | 5篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 1篇 |
排序方式: 共有1410条查询结果,搜索用时 31 毫秒
21.
关于药物在机体内的跨膜转运机制,以往的研究多侧重于药物理化性质.近年,发现体内存在多种转运蛋白(转运体)系统,对药物体内跨膜转运,有重要意义,有时甚至起决定性作用,因此,药物转运体对药物的体内过程,即药物的吸收、分布、代谢和排泄及药物之间的相互作用有重要影响,并可影响或决定药物的动力学过程. 相似文献
22.
23.
Callie Drennen Erin Gorse Robert E. Stratford 《Journal of pharmaceutical sciences》2018,107(4):1194-1203
Pharmacokinetic modeling was used to describe 5 (and 6)-carboxy-2′,7′-dichloroflourescein (CDF) disposition in Caco-2 cells following CDF or CDFDA (CDF diacetate) dosing. CDF transcellular flux was modeled by simple passive diffusion. CDFDA dosing models were based on simultaneous fitting of CDF levels in apical, basolateral, and intracellular compartments. Predicted CDF efflux was 50% higher across the apical versus the basolateral membrane. This difference was similar following apical and basolateral CDFDA dosing, despite intracellular levels being 3-fold higher following basolateral dosing, thus supporting nonsaturable CDF efflux kinetics. A 3-compartment catenary model with intracellular CDFDA hydrolysis described CDF disposition. This model predicted that apical CDF efflux was not altered in the presence of MK-571, and that basolateral membrane clearance was enhanced to account for reduced intracellular CDF in the presence of this multidrug resistance-associated protein (MRP) inhibitor. Similar effects were predicted for glyceollin, while genistein exposure had no predicted effects on CDF efflux. These modulator effects are discussed in the context of model predicted intracellular CDF concentrations relative to reports of CDF affinity (measured by Km) for MRP2 and MRP3. This model-based analysis confirms the complexity of efflux kinetics and suggests that other transporters may have contributed to CDF efflux. 相似文献
24.
The response of T cells in relation to the cell cycle has not been extensively studied. We have attempted to address this question using Jurkat T cells treated with cytostatic drugs known to arrest cells at various transition points of their cycle. We tested several concentrations of drugs that act at G1/S (hydroxyurea, lovastatin, thymidine), early S (aphidicolin, cyclosporin A, rapamycin) or G2+M (colchicine, nocodazole) in 24 h cultures. Cytofluorimetric analyses showed that cycling Jurkat cells were equally distributed between the G1 (44.9 ± 6.5%) and S (42.3 ± 8.0%) phases. Cell distribution in G2+M was 12.7 ± 2.8%. Hydroxyurea but not lovastatin increased the percentage of cells in S phase to ≈60–70% and both drugs decreased it to ≈30% in G1. Thymidine had no effects. Aphidicolin increased the distribution in S phase to ≈70% with a decrease in G1 to ≈30%. Cyclosporin A and rapamycin increased the percentage of the cells in G1 to ≈70% and decreased it to ≈25% in S phase. Nocodazole increased cell distribution in G2+M to ≈60% and induced a decrease in G1 to ≈10%. The effects of the drugs were not related to their toxicity and their limited efficiency raised the possibility that Jurkat cells possessed an intrinsic resistance to these xenobiotics. Time-course analysis showed (scanning electron microscopy) that the early morphological changes induced by colchicine were reversible. Drug efflux experiments (vinblastine) suggested that an ATP-dependent process could be involved. However, Northern blot analyses showed a weak signal for MDR1 (P-glycoprotein). In contrast, a probe for MRP (P-190) showed a strong signal in Jurkat and peripheral lymphocytes. The presence of drugs (cyclosporin A, nocodazole, thymidine) (24 h) did not upregulate its message and cell treatment with
-butathione (S,R)-sulfoximine only moderately affected the efficiency of the glutathione S-conjugate MRP transporter. Our data suggest that the intrinsic multidrug resistance of leukemic Jurkat T cells does not appear to involve the MDR1 and MRP members of the ABC family of reverse drug transporters and these observations raise the possibility of the involvement of multifaceted mechanisms. 相似文献
25.
26.
ATP结合盒转运体在肝癌多药耐药中的研究进展 总被引:1,自引:0,他引:1
肝癌是我国常见的恶性肿瘤之一,手术切除率低,术后复发率高,故对于进展期肝癌患者来说,化疗显得迫切需要。然而,多药耐药性(MDR)是化疗的最大障碍。ATP结合盒转运体介导的多药耐药是肝癌化疗失败的主要原因,因此针对ATP结合盒转运体(ABC)的肿瘤MDR逆转策略,对于提高肝癌化疗效果具有十分重要的意义。该文针对ABC介导的耐药机制及目前克服MDR的一些新策略予以综述。 相似文献
27.
28.
目的研究胡芦巴对小肠主要胆固醇载体ABCG5/G8、ABCA1、SR-B1和NPC1L1在Caco-2细胞基因表达的影响,探讨其降脂机制。方法将胡芦巴水溶液暴露于Caco-2细胞中24和48h作为治疗组,未加药者为对照组,从细胞中分离mRNA,进行Real-Time PCR分析,以GAPDH为内部标准测定ABCG5/G8,ABCA1和NPC1L1基因的表达。结果胡芦巴可以抑制胆固醇载体ABCG5(90%)/G8(80%)、ABCA1(70%)、SR-B1(70%)和NPC1L1(70%)表达。结论胡芦巴可抑制Caco-2细胞胆固醇载体的基因表达水平。 相似文献
29.
Kerstin Kanonenberg Christian K.W. Schwarz Lutz Schmitt 《Research in microbiology》2013,164(6):596-604
Secretion is an essential task for prokaryotic organisms to interact with their surrounding environment. In particular, the production of extracellular proteins and peptides is important for many aspects of an organism's survival and adaptation to its ecological niche. In Gram-negative bacteria, six different protein secretion systems have been identified so far, named Type I to Type VI; differing greatly in their composition and mechanism of action (Economou et al., 2006). The two membranes present in Gram-negative bacteria are negotiated either by one-step transport mechanisms (Type I and Type III), where the unfolded substrate is translocated directly into the extracellular space, without any periplasmic intermediates, or by two-step mechanisms (Type II and Type V), where the substrate is first transported into the periplasm to allow folding before a second transport step across the outer membrane occurs. Here we focus on Type I secretion systems and summarise our current knowledge of these one-step transport machineries with emphasis on the N-terminal extensions found in many Type I-specific ABC transporters. ABC transporters containing an N-terminal C39 peptidase domain cut off a leader peptide present in the substrate prior to secretion. The function of the second type of appendix, the C39 peptidase-like domain (CLD), is not yet completely understood. Recent results have shown that it is nonetheless essential for secretion and interacts specifically with the substrate of the transporter. The third group present does not contain any appendix. In light of this difference we compare the function of the appendix and the differences that might exist among the three families of T1SS. 相似文献
30.