全文获取类型
收费全文 | 1796篇 |
免费 | 94篇 |
国内免费 | 78篇 |
出版年
2023年 | 23篇 |
2022年 | 33篇 |
2021年 | 46篇 |
2020年 | 33篇 |
2019年 | 56篇 |
2018年 | 78篇 |
2017年 | 46篇 |
2016年 | 36篇 |
2015年 | 56篇 |
2014年 | 83篇 |
2013年 | 163篇 |
2012年 | 92篇 |
2011年 | 180篇 |
2010年 | 81篇 |
2009年 | 87篇 |
2008年 | 86篇 |
2007年 | 86篇 |
2006年 | 66篇 |
2005年 | 46篇 |
2004年 | 56篇 |
2003年 | 58篇 |
2002年 | 42篇 |
2001年 | 21篇 |
2000年 | 21篇 |
1999年 | 19篇 |
1998年 | 16篇 |
1997年 | 15篇 |
1996年 | 18篇 |
1995年 | 14篇 |
1994年 | 19篇 |
1993年 | 24篇 |
1992年 | 14篇 |
1991年 | 13篇 |
1990年 | 16篇 |
1989年 | 11篇 |
1988年 | 10篇 |
1987年 | 6篇 |
1986年 | 7篇 |
1985年 | 21篇 |
1984年 | 31篇 |
1983年 | 18篇 |
1982年 | 27篇 |
1981年 | 19篇 |
1980年 | 19篇 |
1979年 | 13篇 |
1978年 | 9篇 |
1977年 | 11篇 |
1975年 | 10篇 |
1974年 | 4篇 |
1973年 | 4篇 |
排序方式: 共有1968条查询结果,搜索用时 250 毫秒
101.
Cyclooxygenase-2 is a very important physiological enzyme playing key roles in various biological functions especially in the mechanism of pain and inflammation, among other roles, making it a molecule of high interest to the pharmaceutical community as a target. COX 2 enzyme is induced only during inflammatory processes or cancer and reflects no role in the guarding stomach lining. Thus, selective COX-2 inhibition can significantly reduce the adverse effects including GI tract damage and hepatotoxic effects of traditional NSAIDs like aspirin, ibuprofen, etc. Recent developments on COX-2 inhibitors is primarily focused on improving the selectivity index of the drug towards COX-2 along with enhancing the potency of the drug by modifying the scaffolds of Coxibs currently in the market like Celecoxib, Indomethacin, Oxaprozin, etc. We have reported the progress on new COX-2 inhibitors in the last decade (2008–2019) focussing on five heterocyclic rings- Pyrazole, Indole, Oxazole, Pyridine and Pyrrole. The addition of various moieties to these core rings and their structure-activity relationship along with their molecular modelling data have been explored in the article. This review aims to aid medicinal chemists in the design and discovery of better COX-2 inhibitors constructed on these five heterocyclic pharmacophores. 相似文献
102.
103.
104.
Mohammad Rouhani Mohammad Amin Samih Mohammad Gorji Bentol Hoda Moradi 《Archives Of Phytopathology And Plant Protection》2019,52(1-2):45-53
The common pistachio psylla, Agonoscena pistaciae (Hemiptera: Aphalaridae) is one of the most detrimental pests to pistachio trees. Nowadays various pesticides are used to control the common pistachio psylla, but extensive pesticide spraying against this pest over a period of several years has overpowered its natural enemies. The plant’s byproducts come as an alternative ecologically more compatible in substitution to the synthetic insecticides. This work aims to evaluate the insecticidal potential of herbal extracts of fruit peels of Citrus sinensis and Citrus reticulata, seeds of C. sinensis and Rubia tinctorum, and leaves of Lawsonia inermis against common pistachio psylla. Five concentration 40, 47, 56, 67 and 80 µl/ml, of these plant extracts were sprayed on the fifth instar nymphs of common pistachio psylla by Potter Spray Tower under laboratory conditions (26?±?2?°C, 60–70% RH and a photoperiod of 16L: 8D h). Results showed significant differences among the treatments of the plant extracts and between the concentrations. The LC50 values of C. sinensis peels, C. reticulata peels, C. sinensis seeds, R. tinctorum seeds and L. inermis leaves were 62.04, 38.84, 43.60, 59.01 and 33.99 µl/ml, respectively. Also, all extracts showed the greatest mortality effect in 80 µl/ml concentration. According to these results, these plant extracts may use as herbal pesticides chemical control programme of common pistachio psylla. 相似文献
105.
Maria Raffaella Greco Emeline Bon Rosa Rubino Lorenzo Guerra Manuel Bernabe-Garcia Stefania Cannone Maria-Luisa Cayuela Loredana Ciaccia Séverine Marionneau-Lambot Thibauld Oullier Gaëlle Fromont Roseline Guibon Sébastien Roger Stephan Joel Reshkin Rosa Angela Cardone 《生物化学与生物物理学报:疾病的分子基础》2019,1865(1):26-37
Metastatic cancer cells are highly plastic for the expression of different tumor phenotype hallmarks and organotropism. This plasticity is highly regulated but the dynamics of the signaling processes orchestrating the shift from one cell phenotype and metastatic organ pattern to another are still largely unknown. The scaffolding protein NHERF1 has been shown to regulate the expression of different neoplastic phenotypes through its PDZ domains, which forms the mechanistic basis for metastatic organotropism. This reprogramming activity was postulated to be dependent on its differential phosphorylation patterns. Here, we show that NHERF1 phosphorylation on S279/S301 dictates several tumor phenotypes such as in vivo invasion, NHE1-mediated matrix digestion, growth and vasculogenic mimicry. Remarkably, injecting mice with cells having differential NHERF1 expression and phosphorylation drove a shift from the predominantly lung colonization (WT NHERF1) to predominately bone colonization (double S279A/S301A mutant), indicating that NHERF1 phosphorylation also acts as a signaling switch in metastatic organotropism. 相似文献
106.
Aarts LH Verkade P Schrama LH Oestreicher AB Gispen WH Schotman P 《Molecular neurobiology》1999,20(1):17-28
B-50 (GAP-43) is an axonal, plasma membrane-associated protein involved in growth cone morphology and function. We have conducted immunocytochemical, electron microscopic, and time-lapse experiments to visualize morphological consequences of local accumulations of B-50 at the plasma membrane of B-50-transfected PC-B2 cells, a clonal PC12 cell line with very low expression of endogenous B-50. The distribution of the transfected B-50 within these cells was inhomogeneous. At sites where the B-50 concentration was locally increased up to twofold, numerous filopodia were present in growth cone-like, substrate-attached regions. When local B-50 concentrations were even higher (up to 6.2-fold), blebs were formed, often containing vesicular structures, heavily decorated with B-50 immunoreactivity. Double labeling with f-actin binding phalloidin revealed that local B-50 accumulations were accompanied by increased actin filament concentrations. Colocalization of B-50 with actin filaments was prominent in filopodia, but was virtually absent in blebs, suggesting a disconnection of the bleb plasma membrane from the actin cytoskeleton. We conclude that B-50 evokes distinct effects on cell-surface activity in PC12 cells depending on its local concentration. 相似文献
107.
108.
The serotonin1A (5-HT1A) receptors are important members of the superfamily of seven transmembrane domain G-protein coupled receptors. They appear to be involved in various behavioral, cognitive and developmental functions. Mammalian cells in culture heterologously expressing membrane receptors represent convenient systems to address problems in receptor biology. We report here the pharmacological characterization of one of the first isolated clones of CHO cells stably expressing the human 5-HT1A receptor using the selective agonist 8-OH-DPAT and antagonist p-MPPF. In addition, we demonstrate that agonist and antagonist binding to the receptor exhibit differential sensitivity to the non-hydrolyzable GTP analogue, GTP--S, as was observed earlier with the native receptor from bovine hippocampus. These results show that the human 5-HT1A receptor expressed in CHO cells displays characteristic features found in the native receptor isolated from bovine hippocampus and promises to be a potentially useful system for future studies of the receptor.These authors have contributed equally to the work 相似文献
109.
Oncogenic ras-p21 directly activates jun-N-terminal kinase (JNK) and its substrate, jun as a unique step on its mitogenic signal transduction pathway. This activation is blocked by the specific JNK-jun inhibitor, glutathione-S-transferase-pi (GST-pi). Four domains of GST-pi have been implicated in this regulatory function: 34-50, 99-121, 165-182, and 194-201. The 34-50 domain is unique in that it does not affect GST-pi binding to JNK-jun but blocks jun phosphorylation by JNK. We now find that it completely blocks oncogenic (Val 12-) ras-p21-induced oocyte maturation but has no effect on insulin-induced oocyte maturation. Because the latter process requires activation of wild-type ras-p21, this peptide appears to be specific for inhibiting only the oncogenic form of ras-p21, suggesting its use in treating ras-induced tumors. 相似文献
110.
Detection of tumor marker CA125 in ovarian carcinoma using quantum dots 总被引:11,自引:0,他引:11
The fluorescent labeling of biological materials usingsmall-molecule organic dyes is widely employed in bio-logical imaging and clinical diagnosis. Organic fluoro-phores, however, have certain characteristics that limittheir advantages in some applications. These limitationsinclude narrow excitation bands and broad emissionbands with red spectral tails, which make the simultaneousevaluation of several light-emitting probes difficult due tospectral overlap. Also, many organic dyes exhibit highp… 相似文献