全文获取类型
收费全文 | 1003篇 |
免费 | 92篇 |
出版年
2021年 | 7篇 |
2020年 | 9篇 |
2019年 | 10篇 |
2018年 | 8篇 |
2017年 | 10篇 |
2016年 | 10篇 |
2015年 | 26篇 |
2014年 | 32篇 |
2013年 | 37篇 |
2012年 | 38篇 |
2011年 | 46篇 |
2010年 | 28篇 |
2009年 | 36篇 |
2008年 | 54篇 |
2007年 | 50篇 |
2006年 | 39篇 |
2005年 | 45篇 |
2004年 | 52篇 |
2003年 | 34篇 |
2002年 | 35篇 |
2001年 | 32篇 |
2000年 | 37篇 |
1999年 | 25篇 |
1998年 | 14篇 |
1997年 | 15篇 |
1996年 | 14篇 |
1995年 | 13篇 |
1994年 | 14篇 |
1993年 | 11篇 |
1992年 | 21篇 |
1991年 | 12篇 |
1990年 | 22篇 |
1989年 | 28篇 |
1988年 | 14篇 |
1987年 | 15篇 |
1986年 | 21篇 |
1985年 | 25篇 |
1984年 | 19篇 |
1983年 | 12篇 |
1982年 | 8篇 |
1981年 | 9篇 |
1980年 | 6篇 |
1979年 | 7篇 |
1978年 | 8篇 |
1977年 | 7篇 |
1975年 | 8篇 |
1973年 | 7篇 |
1971年 | 8篇 |
1970年 | 6篇 |
1960年 | 8篇 |
排序方式: 共有1095条查询结果,搜索用时 15 毫秒
81.
Investigating the phase behavior of sugars in ice and lyophilized solids is of significant interest in the pharmaceutical industry. In this study, Raman and near infrared (NIR) spectroscopy are used to characterize and quantitate trehalose crystallization using several chemometric models. The predictive behaviors of partial least squares (PLS), principal component analysis (PCA), and multiple linear regression (MLR) models are compared. In general, PLS and PCA outperform linear and MLR models. Changes in specific vibrational modes associated with several coupled motions are described and assigned as a function of crystal content. In addition to characterization and quantitation, our method may be used to localize gradients of amorphous and/or crystallized trehalose within a sample. 相似文献
82.
83.
In clinical neurology, a comprehensive understanding of consciousness has been regarded as an abstract concept - best left
to philosophers. However, times are changing and the need to clinically assess consciousness is increasingly becoming a real-world,
practical challenge. Current methods for evaluating altered levels of consciousness are highly reliant on either behavioural
measures or anatomical imaging. While these methods have some utility, estimates of misdiagnosis are worrisome (as high as
43%) - clearly this is a major clinical problem. The solution must involve objective, physiologically based measures that
do not rely on behaviour. This paper reviews recent advances in physiologically based measures that enable better evaluation
of consciousness states (coma, vegetative state, minimally conscious state, and locked in syndrome). Based on the evidence
to-date, electroencephalographic and neuroimaging based assessments of consciousness provide valuable information for evaluation
of residual function, formation of differential diagnoses, and estimation of prognosis. 相似文献
84.
Robinson MW Greig R Beattie KA Lamont DJ Connolly B 《International journal for parasitology》2007,37(2):139-148
The nematodes Trichinella spiralis and Trichinella pseudospiralis are both intracellular parasites of skeletal muscle cells and induce profound alterations in the host cell resulting in a re-alignment of muscle-specific gene expression. While T. spiralis induces the production of a collagen capsule surrounding the host-parasite complex, T. pseudospiralis exists in a non-encapsulated form and is also characterised by suppression of the host inflammatory response in the muscle. These observed differences between the two species are thought to be due to variation in the proteins excreted or secreted (ES proteins) by the muscle larva. In this study, we use a global proteomics approach to compare the ES protein profiles from both species and to identify individual T. pseudospiralis proteins that complement earlier studies with T. spiralis. Following two-dimensional gel electrophoresis, tandem mass spectrometry was used to identify the peptide spots. In many cases identification was aided by the determination of partial peptide sequence from selected mass ions. The T. pseudospiralis spots identified included the major secreted glycoproteins and the secreted 5'-nucleotidase. Furthermore, two major groups of T. spiralis-specific proteins and several T. pseudospiralis-specific proteins were identified. Our results demonstrate the value of proteomics as a tool for the identification of ES proteins that are differentially expressed between Trichinella species and as an aid to identifying key parasite proteins that are involved in the host-parasite interaction. The value of this approach will be further enhanced by data arising out the current T. spiralis genome sequencing project. 相似文献
85.
Chiu G Li S Connolly PJ Pulito V Liu J Middleton SA 《Bioorganic & medicinal chemistry letters》2007,17(12):3292-3297
Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms (BPH/LUTS) can be effectively treated by alpha(1)-adrenergic receptor antagonists. Unfortunately, all currently marketed alpha(1) blockers produced CV related side effects that are caused by the subtype non-selective nature of the drugs. To overcome this problem, it was postulated that a alpha(1a/1d) subtype selective antagonist would bring more benefit for the treatment of BPH/LUTS. In developing selective alpha(1a/1d) ligands, (arylpiperazinyl)cyclohexylsulfonamides were synthesized and their binding profiles against three cloned human alpha(1)-adrenergic receptor subtypes were evaluated. Many compounds show equal affinity for both alpha(1a) and alpha(1d) subtypes with good selectivity against the alpha(1b) subtype. They also overcome the problem of dopamine receptor affinity that previous analogues had exhibited. 相似文献
86.
Huang S Lin R Yu Y Lu Y Connolly PJ Chiu G Li S Emanuel SL Middleton SA 《Bioorganic & medicinal chemistry letters》2007,17(5):1243-1245
The novel compound 3-(1H-benzimidazol-2-yl)-5-isoquinolin-4-ylpyrazolo[1,2-b]pyridine was discovered to be a potent CDK1 inhibitor. Described here is the chemistry for its synthesis, including Pd(II) catalyzed Stille coupling reaction and sulfur(0) induced benzimidazole formation. Its effects on VEGFR-2 kinase activity and tumour cell proliferation are also described. 相似文献
87.
Lin R Connolly PJ Lu Y Chiu G Li S Yu Y Huang S Li X Emanuel SL Middleton SA Gruninger RH Adams M Fuentes-Pesquera AR Greenberger LM 《Bioorganic & medicinal chemistry letters》2007,17(15):4297-4302
A series of 3,5-disubstituted pyrazolo[3,4-b]pyridine cyclin-dependent kinase (CDK) inhibitors was synthesized. These compounds showed potent and selective CDK inhibitory activities and inhibited in vitro cellular proliferation in cultured human tumor cells. Selected compounds were evaluated in an in vivo tumor xenograft model. The synthesis and biological evaluation of these pyrazolo[3,4-b]pyridines and related compounds are reported. 相似文献
88.
Li S Chiu G Pulito VL Liu J Connolly PJ Middleton SA 《Bioorganic & medicinal chemistry letters》2007,17(6):1646-1650
Subtype-selective alpha-1a and/or alpha-1d adrenergic receptor antagonists may be useful for the treatment of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) with fewer adverse effects than non-selective drugs. A series of 1-arylpiperazinyl-4-cyclohexylamine derived isoindole-1,3-diones has been synthesized, displaying in vitro alpha(1a) and alpha(1d) binding affinity K(i) values in the range of 0.09-38nM with K(i)(alpha1b)/K(i)(alpha1a) and K(i)(alpha1b)/K(i)(alpha1d) selectivity ratios up to 3607-fold. 相似文献
89.
Lin R Chiu G Yu Y Connolly PJ Li S Lu Y Adams M Fuentes-Pesquera AR Emanuel SL Greenberger LM 《Bioorganic & medicinal chemistry letters》2007,17(16):4557-4561
Two series of 3,4-disubstituted pyrazole analogues, 3-(benzimidazol-2-yl)-4-[2-(pyridin-3-yl)-vinyl]-pyrazoles (2) and 3-(imidazol-2-yl)-4-[2-(pyridin-3-yl)-vinyl]-pyrazoles (3), were synthesized as novel cyclin-dependent kinase (CDK) inhibitors. Representative compounds showed potent and selective CDK inhibitory activities and inhibited in vitro cellular proliferation in various human tumor cells. The design, synthesis, and preliminary biological evaluation of these pyrazole compounds are reported. 相似文献
90.
A plant triterpenoid, avicin D, induces autophagy by activation of AMP-activated protein kinase 总被引:2,自引:0,他引:2
Xu ZX Liang J Haridas V Gaikwad A Connolly FP Mills GB Gutterman JU 《Cell death and differentiation》2007,14(11):1948-1957
Avicins, a family of plant triterpene electrophiles, can trigger apoptosis-associated tumor cell death, and suppress chemical-induced carcinogenesis by its anti-inflammatory, anti-mutagenic, and antioxidant properties. Here, we show that tumor cells treated with benzyloxycarbonylvalyl-alanyl-aspartic acid (O-methyl)-fluoro-methylketone, an apoptosis inhibitor, and Bax(-/-)Bak(-/-) apoptosis-resistant cells can still undergo cell death in response to avicin D treatment. We demonstrate that this non-apoptotic cell death is mediated by autophagy, which can be suppressed by chloroquine, an autophagy inhibitor, and by specific knockdown of autophagy-related gene-5 (Atg5) and Atg7. Avicin D decreases cellular ATP levels, stimulates the activation of AMP-activated protein kinase (AMPK), and inhibits mammalian target of rapamycin (mTOR) and S6 kinase activity. Suppression of AMPK by compound C and dominant-negative AMPK decreases avicin D-induced autophagic cell death. Furthermore, avicin D-induced autophagic cell death can be abrogated by knockdown of tuberous sclerosis complex 2 (TSC2), a key mediator linking AMPK to mTOR inhibition, suggesting that AMPK activation is a crucial event targeted by avicin D. These findings indicate the therapeutic potential of avicins by triggering autophagic cell death. 相似文献