全文获取类型
收费全文 | 1073篇 |
免费 | 74篇 |
专业分类
1147篇 |
出版年
2023年 | 11篇 |
2022年 | 19篇 |
2021年 | 36篇 |
2020年 | 21篇 |
2019年 | 10篇 |
2018年 | 26篇 |
2017年 | 14篇 |
2016年 | 32篇 |
2015年 | 45篇 |
2014年 | 48篇 |
2013年 | 69篇 |
2012年 | 91篇 |
2011年 | 76篇 |
2010年 | 47篇 |
2009年 | 38篇 |
2008年 | 63篇 |
2007年 | 42篇 |
2006年 | 36篇 |
2005年 | 40篇 |
2004年 | 29篇 |
2003年 | 33篇 |
2002年 | 19篇 |
2001年 | 32篇 |
2000年 | 16篇 |
1999年 | 16篇 |
1998年 | 5篇 |
1997年 | 7篇 |
1996年 | 5篇 |
1995年 | 7篇 |
1994年 | 7篇 |
1993年 | 5篇 |
1992年 | 13篇 |
1991年 | 12篇 |
1990年 | 17篇 |
1989年 | 9篇 |
1988年 | 14篇 |
1987年 | 12篇 |
1986年 | 9篇 |
1985年 | 12篇 |
1984年 | 6篇 |
1982年 | 8篇 |
1981年 | 4篇 |
1980年 | 9篇 |
1979年 | 13篇 |
1978年 | 4篇 |
1973年 | 13篇 |
1972年 | 11篇 |
1971年 | 9篇 |
1970年 | 6篇 |
1966年 | 3篇 |
排序方式: 共有1147条查询结果,搜索用时 15 毫秒
101.
Das B Rudra S Yadav A Ray A Rao AV Srinivas AS Soni A Saini S Shukla S Pandya M Bhateja P Malhotra S Mathur T Arora SK Rattan A Mehta A 《Bioorganic & medicinal chemistry letters》2005,15(19):4261-4267
Novel oxazolidinones were synthesized containing a number of substituted five-membered heterocycles attached to the 'piperazinyl-phenyl-oxazolidinone' core of eperezolid. Further, the piperazine ring of the core was replaced by other diamino-heterocycles. These modifications led to several compounds with potent activity against a spectrum of resistant and susceptible gram-positive organisms, along with the identification of ranbezolid (RBx 7644) as a clinical candidate. 相似文献
102.
Arora J Bordeleau M Dube L Jarvie K Mazzocco L Peragine J Tehim A Egle I 《Bioorganic & medicinal chemistry letters》2005,15(23):5253-5256
A series of N-[(3S)-1-benzylpyrrolidin-3-yl]-(2-thienyl)benzamides 8 has been prepared and found to bind with high affinity to the human D(4) (hD(4)) and 5-HT(2A) receptors. Several compounds displayed selectivity for these receptors versus hD(2) and alpha(1) adrenergic receptors of over 500-fold. 相似文献
103.
Kamal A Hari Babu A Venkata Ramana A Sinha R Yadav JS Arora SK 《Bioorganic & medicinal chemistry letters》2005,15(7):1923-1926
The preparation and antitubercular properties of a series of phthalimido- and naphthalimido-linked phenazines are described. Some of these new compounds inhibited the growth of Mycobacterium tuberculosis ATCC 27294, Mycobacterium avium ATCC 49601, Mycobacterium intracellulare ATCC 13950 and some clinical isolates. 相似文献
104.
Dahl JL Arora K Boshoff HI Whiteford DC Pacheco SA Walsh OJ Lau-Bonilla D Davis WB Garza AG 《Journal of bacteriology》2005,187(7):2439-2447
The modification of metabolic pathways to allow for a dormant lifestyle appears to be an important feature for the survival of pathogenic bacteria within their host. One regulatory mechanism for persistent Mycobacterium tuberculosis infections is the stringent response. In this study, we analyze the stringent response of a nonpathogenic, saprophytic mycobacterial species, Mycobacterium smegmatis. The use of M. smegmatis as a tool for studying the mycobacterial stringent response was demonstrated by measuring the expression of two M. tuberculosis genes, hspX and eis, in M. smegmatis in the presence and absence of rel(Msm). The stringent response plays a role in M. smegmatis cellular and colony formation that is suggestive of changes in the bacterial cell wall structure. 相似文献
105.
Mao L Yang L Arora A Choe ES Zhang G Liu Z Fibuch EE Wang JQ 《The Journal of biological chemistry》2005,280(13):12602-12610
The regulation of protein phosphorylation requires coordinated interaction between protein kinases and protein phosphatases (PPs). Recent evidence has shown that the Galphaq-protein-coupled metabotropic glutamate receptor (mGluR) 5 up-regulates phosphorylation of MAPK/ERK1/2. However, signaling mechanisms linking mGluR5 to ERK are poorly understood. In this study, roles of a major serine/threonine PP, PP2A, in this event were evaluated in cultured neurons. We found that the PP1/2A inhibitors okadaic acid and calyculin A mimicked the effect of the mGluR5 agonists (RS)-3,5-dihydroxyphenylglycine and (RS)-2-chloro-5-hydroxyphenylglycine in facilitating phosphorylation of ERK1/2 and its upstream kinase, MEK1/2, in a PP2A-dependent but not PP1-dependent manner. Co-administration of either inhibitor with an mGluR5 agonist produced additive phosphorylation of ERK1/2. Enzymatic assays showed a basal level of phosphatase activity of PP2A under normal conditions, and activation of mGluR5 selectively inhibited PP2A, but not PP1, activity. In addition, a physical association of the cytoplasmic C terminus of mGluR5 with PP2A was observed, and ligand activation of mGluR5 reduced mGluR5-PP2A binding. Additional mechanistic studies revealed that mGluR5 activation increased tyrosine (Tyr307) phosphorylation of PP2A, which was dependent on activation of a p60c-Src family tyrosine kinase, but not the epidermal growth factor receptor tyrosine kinase and resulted in dissociation of PP2A from mGluR5 and reduced PP2A activity. Together, we have identified a novel, mGluR5-triggered signaling mechanism involving use- and Src-dependent inactivation of PP2A, which contributes to mGluR5 activation of MEK1/2 and ERK1/2. 相似文献
106.
Distinct roles for IL-4 and IL-10 in regulating T2 immunity during allergic bronchopulmonary mycosis 总被引:3,自引:0,他引:3
Hernandez Y Arora S Erb-Downward JR McDonald RA Toews GB Huffnagle GB 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(2):1027-1036
Pulmonary Cryptococcus neoformans infection of C57BL/6 mice is an established model of an allergic bronchopulmonary mycosis that has also been used to test a number of immunomodulatory agents. Our objective was to determine the role of IL-4 and IL-10 in the development/manifestation of the T2 response to C. neoformans in the lungs and lung-associated lymph nodes. In contrast to wild-type (WT) mice, which develop a chronic infection, pulmonary clearance was significantly greater in IL-4 knockout (KO) and IL-10 KO mice but was not due to an up-regulation of a non-T cell effector mechanism. Pulmonary eosinophilia was absent in both IL-4 KO and IL-10 KO mice compared with WT mice. The production of IL-4, IL-5, and IL-13 by lung leukocytes from IL-4 KO and IL-10 KO mice was lower but IFN-gamma levels remained the same. TNF-alpha and IL-12 production by lung leukocytes was up-regulated in IL-10 KO but not IL-4 KO mice. Overall, IL-4 KO mice did not develop the systemic (lung-associated lymph nodes and serum) or local (lungs) T2 responses characteristic of the allergic bronchopulmonary C. neoformans infection. In contrast, the systemic T2 elements of the response remained unaltered in IL-10 KO mice whereas the T2 response in the lungs failed to develop indicating that the action of IL-10 in T cell regulation was distinct from that of IL-4. Thus, although IL-10 has been reported to down-regulate pulmonary T2 responses to isolated fungal Ags, IL-10 can augment pulmonary T2 responses if they occur in the context of fungal infection. 相似文献
107.
A quantitative structure-activity relationship (QSAR) study has been made on some series of anti-hepatitis B virus (HBV) agents, namely, a series of novel bis(L-amino acid) ester prodrugs of 9-[2--(phosphonomethoxy)ethyl]adenine, a similar series of compounds comprising of 2- amino-6-arylthio-9-[2-(phosphonoethoxy)ethyl] purine bis(2,2,2- trifluoroethyl) esters, and a series of 1-isopropylsulfonyl-2-amine benzimidazoles. In each case significant correlations are found between the anti-HBV potencies and some physicochemical and steric properties of the compounds, indicating that for the first two series the activity is controlled by the hydrophobic and the bulk properties of the molecules and, for the third series, the steric and hydrogen bonding properties of compounds are crucial for their anti-HBV potency. 相似文献
108.
Khanna N Arora D Halder S Mehta AK Garg GR Sharma SB Mahajan P 《Indian journal of experimental biology》2010,48(3):299-305
Treatment with C. mukul and O. sanctum, showed a significant decrease in cholesterol and triglyceride levels respectively. O. sanctum also significantly increased serum HDL-cholesterol compared to control. Serum MDA levels were significantly reduced in all the treated groups compared to control suggesting that each of the drugs under study were effective in their free radical scavenging action. Erythrocyte SOD activity was increased in all the treatment groups with C. mukul showing the maximum effect followed by O. sanctum, folic acid and ramipril. The erythrocyte CAT activity was significantly increased in all the drug treated groups with maximum increase seen in O. sanctum and ramipril treated groups, whereas lesser effects were observed with C. mukul and folic acid groups. Thus, the indigenous drugs, C. mukul and O. sanctum had beneficial effect on hypercholesterolemic rabbit model, both in terms of lipid profile as well as antioxidant potential. Ocimum sanctum was found to be the most promising of all the drugs. Moreover, it could be hypothesized that these plant products along with folic acid and ramipril can be explored for synergistic effect for treatment for hypercholesterolemic conditions. 相似文献
109.
The present study examines the role of cerebroventricular administered (IIIrd ventricle) galanin on LHRH and LH release in adult and immature male rats. In both age groups, galanin stimulated LHRH synthesis and release from the hypothalamus, leading to a higher release of pituitary LH which in turn increased plasma LH levels. Galantide, a galanin receptor blocker, on the other hand, drastically reduced hypothalamic LHRH and plasma LH while increasing pituitary LH. In vitro incubation of anterior pituitary cells with galanin followed by LHRH resulted in increased release of pituitary LH but not by galanin alone. Galantide exhibited no such effect either alone or with LHRH. These results indicate that galanin is an important regulator for both hypothalamic LHRH and hypophysial LH and its role is independent of age in the case of male rats. 相似文献
110.
Usha Singh Ajit Kumar Rajesh Sinha Sushma Manral Shvetambri Arora Sant Ram Rakesh K. Mishra Prachi Gupta Surendra K. Bansal Ashok K. Prasad Shyam Biswal Virinder S. Parmar Hanumantharao G. Raj 《Chemico-biological interactions》2010,185(3):263-270
Polyphenols, coumarin (1,2-benzopyrone) and chromone (1,4-benzopyrone), are naturally occurring constituent of variety of plant species. They have attracted immense interest because of their diverse pharmacological activities. Not much was known about biological activities of acetyl derivative (polyphenolic acetates) of parent polyphenols. In previous investigations, we have conclusively established calreticulin transacetylase catalyzed activation of endothelial nitric oxide synthase (eNOS) by polyphenolic acetates. In the present work, calreticulin transacetylase of human peripheral blood mononuclear cells was characterized with respect to specificity for various polyphenolic acetates and its role in the activation of TNF-α induced nitric oxide synthase (iNOS). Peripheral blood mononuclear cells incubated with a model polyphenolic acetate, 7,8-diacetoxy-4-methylcoumarin (DAMC), along with l-arginine caused activation of NOS. The incubation of peripheral blood mononuclear cells with TNF-α and DAMC resulted in increased production of NO as compared to TNF-α alone. This increased NO production was attenuated by l-Nω-nitro-l-arginine methyl ester (l-NAME), a well known non-specific inhibitor of NOS, and 1400W (N-[3-(aminomethyl) benzyl] acetamidine), a specific inhibitor of human iNOS. These results substantiate the CRTAase catalyzed activation of iNOS. Further, expression of NOS isoforms by semi-quantitative PCR and real-time RT-PCR confirms the preponderance of iNOS in TNF-α treated peripheral blood mononuclear cells over the untreated one. It was also observed that polyphenolic acetates inhibit TNF-α mediated release of IL-6 from peripheral blood mononuclear cells. 相似文献