全文获取类型
收费全文 | 714篇 |
免费 | 60篇 |
国内免费 | 18篇 |
专业分类
儿科学 | 2篇 |
妇产科学 | 4篇 |
基础医学 | 138篇 |
口腔科学 | 6篇 |
临床医学 | 38篇 |
内科学 | 77篇 |
皮肤病学 | 14篇 |
神经病学 | 61篇 |
特种医学 | 17篇 |
外科学 | 19篇 |
综合类 | 40篇 |
预防医学 | 26篇 |
眼科学 | 2篇 |
药学 | 281篇 |
中国医学 | 4篇 |
肿瘤学 | 63篇 |
出版年
2023年 | 8篇 |
2022年 | 7篇 |
2021年 | 18篇 |
2020年 | 27篇 |
2019年 | 14篇 |
2018年 | 23篇 |
2017年 | 26篇 |
2016年 | 23篇 |
2015年 | 30篇 |
2014年 | 38篇 |
2013年 | 85篇 |
2012年 | 30篇 |
2011年 | 44篇 |
2010年 | 42篇 |
2009年 | 28篇 |
2008年 | 41篇 |
2007年 | 29篇 |
2006年 | 25篇 |
2005年 | 25篇 |
2004年 | 29篇 |
2003年 | 31篇 |
2002年 | 17篇 |
2001年 | 11篇 |
2000年 | 14篇 |
1999年 | 12篇 |
1998年 | 10篇 |
1997年 | 14篇 |
1996年 | 9篇 |
1995年 | 11篇 |
1994年 | 12篇 |
1993年 | 3篇 |
1992年 | 10篇 |
1991年 | 6篇 |
1990年 | 1篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1987年 | 7篇 |
1986年 | 3篇 |
1985年 | 5篇 |
1984年 | 7篇 |
1983年 | 1篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 2篇 |
排序方式: 共有792条查询结果,搜索用时 171 毫秒
91.
A S Lippa C A Klepner L Yunger M C Sano W V Smith B Beer 《Pharmacology, biochemistry, and behavior》1978,9(6):853-856
The in vitro and in vivo ability of benzodiazepines to inhibit specific 3H-diazepam binding correlated with their ability to increase punished responding in a conflict situation. Conflict and foot shock, the punishing stimulus used in most conflict procedures, also altered 3H-diazepam binding. These data implicate 3H-diazepam binding sites in mediating at least some of the anxiolytic properties of benzodiazepines and suggest the existence of some endogenous substance which might be involved in the etiology of anxiety. 相似文献
92.
JL Mokrosz B Duszyńska S Charakchieva-Minol AJ Bojarski MJ Mokrosz RL Wydra L Janda L Strekowski 《European journal of medicinal chemistry》1996,31(12):973-980
New N-methylpiperazino-substituted quinazolines 8 and 9, phthalazine 13, and quinoline 19 have been synthesized. The receptor binding profiles (α1, 5-HT1A, 5-HT2A) of these compounds and their analogs (7–22) have been determined. It has been demonstrated that orientation of a local dipole moment of the heteroaromatic ring system affects both the α1 and 5-HT2A affinity of the investigated class of ligands. Distortion of the coplanar unfused heteroaromatic ring system results in a decreased 5-HT2A affinity. 4-(4-Methylpiperazino)-2-(2-thienyl)quinoline 18 is the most active and selective α1 ligand (Ki = 4.9 nM) with a much lower affinity for 5-HT1A (Ki = 3420 nM) and 5-HT2A (Ki = 211 nM) receptors. 相似文献
93.
Joubert J van Dyk S Green IR Malan SF 《European journal of medicinal chemistry》2011,46(10):5010-5020
A series of polycyclic fluorescent ligands were synthesised and evaluated in murine striatal synaptoneurosomes for N-methyl-d-aspartate receptor (NMDAR) mediated calcium flux inhibition and inhibition of calcium influx through voltage gated calcium channels (VGCC). Amantadine (a) and N-(1-adamantyl)-1,3-propanediamine (c) substituted with 1-cyanoisoindole (3), indazole (5), dinitrobenzene (7, 8), dansyl (9, 10) and coumarin (11) moieties showed moderate to high inhibition of the NMDAR. A high degree of VGCC inhibition was observed for the cyanoisoindole compounds (3, 4) the dansyl compounds (9, 10) and the coumarin compound (12). Fluorophores conjugated to hydroxy-4-aza-8-oxoheptacyclotetradecane (13, 14) did not exhibit any significant VGCC inhibition, but the indazole conjugate (14) showed promising NMDAR activity. Dose response curves were calculated for selected NMDAR inhibitors (8-11) and N-[3-(1-adamantylamino)propyl]-5-dimethylaminonaphthalene-1-sulfonamide (10) exhibited the highest activity of the novel compounds. Compound 10 was further used as a fluorescent NMDAR ligand in a fluorescent competition assay utilizing MK-801, NGP1-01 and amantadine as known NMDAR inhibitors to demonstrate the possible applications of the novel fluorescent compounds. These small molecule fluorescent ligands can be considered as possible pharmacological tools in assay development and/or other investigations in the study of neurodegeneration. 相似文献
94.
Metastatic spreading is a dreadful complication of neoplastic diseases that is responsible for most deaths due to cancer. It consists in the formation of secondary neoplasms from cancer cells that have detached from the primary site. The formation of these secondary sites is not random and several clinical observations indicate that the metastatic colonization exhibits organ selectivity. This organ tropism relies mostly on the complementary adhesive interactions between the cancer cells and their microenvironment. In particular, several lines of evidence suggest that the organ selectivity of colon cancer cells for the liver involves the binding of the circulating cancer cells to endothelial E-selectin. The aim of this review is to make an integrative up-date of the mechanisms that govern the organ selectivity of the metastatic process focusing more especially on the role of selectins and selectin ligands. 相似文献
95.
Iskandarsyah Tejo BA Tambunan US Verkhivker G Siahaan TJ 《Chemical biology & drug design》2008,72(1):27-33
Lymphocyte function-associated antigen-1 (LFA-1)/intercellular adhesion molecule-1 (ICAM-1) interaction plays an important role in the formation of the immunological synapse between T cells and antigen-presenting cells. Blocking of LFA-1/ICAM-1 interactions has been shown to suppress the progression of autoimmune diseases. cIBR peptide (cyclo(1,12)PenPRGGSVLVTGC) inhibits ICAM-1/LFA-1 interaction by binding to the I-domain of LFA-1. To increase the bioactivity of cIBR peptide, we systemically modified the structure of the peptide by (i) replacing the Pen residue at the N-terminus with Cys, (ii) cyclization using amide bond formation between Lys-Glu side chains, and (iii) reducing the peptide size by eliminating the C-terminal residue. We found that the activity of cIBR peptide was not affected by replacing Phe with Cys. Peptide cyclization by forming the Lys-Glu amide bond also increased the activity of cIBR peptide, presumably due to the resistance of the amide bond to the reducing nature of glutathione in plasma. We also found that a reduced derivative of cIBR with eight residues (cyclo(1,8)CPRGGSVC) has a bioactivity similar to that of the larger cIBR peptides. Our findings suggest that, by systemically modifying the structure of cIBR peptide, the biological activity of these derivatives can be optimized for future use to inhibit T-cell adhesion in in vivo models of autoimmune diseases. 相似文献
96.
The importance of Toll-like receptors (TLRs) in stimulating innate and adaptive immunity is now well established. In view of this, TLR ligands have become interesting targets to use as stand-alone immunotherapeutics or vaccine adjuvants for cancer treatment. TLR7 and TLR8 were found to be closely related, sharing their intracellular endosomal location, as well as their ligands. In this review, we describe the agonists of TLR7 and TLR8 that are known so far, as well as their contribution to antitumor responses by affecting immune cells, tumor cells, and the tumor microenvironment. The major benefit of TLR7/8 agonists as immune response enhancers is their simultaneous stimulation of several cell types, resulting in a mix of activated immune cells, cytokines and chemokines at the tumor site. We discuss the studies that used TLR7/8 agonists as stand-alone immunotherapeutics or cancer vaccine adjuvants, as well as the potential of TLR7/8 ligands to enhance antitumor responses in passive immunotherapy approaches. 相似文献
97.
Vyshkina T Sylvester A Sadiq S Bonilla E Perl A Kalman B 《Journal of neuroimmunology》2008,200(1-2):145-152
This follow up study aims to refine the roles of previously suggested candidate genes (CC chemokine ligands or CCLs) in multiple sclerosis (MS), and to test these markers in another autoimmune disorder, systemic lupus erythematosus (SLE). After stringent correction for multiple testing, we reject the importance of previously suggested borderline associations with CCLs in MS. A new finding is the differential distribution of CCL8 marker alleles and a haplotype in extreme severity subgroups of MS. In SLE, this study reveals strong associations with a marker and a haplotype encompassing the CCL14 gene, which suggests that a lupus relevant variant may lie within or in the proximity of this haplotype. 相似文献
98.
O. V. Zhuk N. Ya. Golovenko V. G. Zin'kovskii 《Bulletin of experimental biology and medicine》1988,105(5):631-634
Department of Physicochemical Pharmacology, A. V. Bogatskii Physicochemical Institute, Academy of Sciences of the Ukrainian SSR, Odessa. (Presented by Academician of the Academy of Medical Sciences of the USSR A. V. Val'dman.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 105, No. 5, pp. 529–531, May, 1988. 相似文献
99.
S J Cooper 《Brain research bulletin》1985,15(4):397-410
A classical approach to the control of food consumption has been to assume separate mechanisms for the arousal to eat, on the one hand, and the satiation of feeding responses, on the other. The present paper is concerned with a single, and a comparatively simple, neuronal mechanism which is endowed with properties to allow the complete determination of the level of feeding, from hyperphagia to anorexia. The model for the control of feeding, which is presented here, draws attention to the benzodiazepine receptor found distributed through the brain, and present in certain hypothalamic nuclei. Recent evidence which characterizes the receptor is reviewed, and the various categories of benzodiazepine receptor ligands are described. Pharmacological data, collected in a palatable food consumption model using non-food-deprived rats, demonstrate that benzodiazepine receptor agonists produce hyperphagia, benzodiazepine receptor inverse agonists produce anorexia, and benzodiazepine receptor antagonists block both effects. Hence, bidirectional control of food intake can be achieved through differential ligand action at a common set of receptors. Speculatively, these data can be extended, if it is assumed that two endogenous ligands exist in the brain which act like benzodiazepine agonist and inverse agonist, respectively. Evidence for the presence in hypothalamic nuclei of endogenous ligands of the latter kind is discussed. Benzodiazepine withdrawal-induced anorexia is also described, and is taken as evidence for the part played by feeding mechanisms in the development of benzodiazepine physical dependence. 相似文献
100.
Peptides serve as effective drugs and contrast agents in the clinic today. However the inherent drawbacks of peptide structures can limit their efficacy as drugs. To overcome this we have been developing new methods to create ‘tailor-made’ peptides and peptide mimetics with improved pharmacological and physical properties. In this work we introduce novel peptide and small molecule conjugated molecules for earlier diagnosis and treatment of melanoma. 相似文献