全文获取类型
收费全文 | 858篇 |
免费 | 36篇 |
出版年
2023年 | 4篇 |
2022年 | 9篇 |
2021年 | 20篇 |
2020年 | 11篇 |
2019年 | 19篇 |
2018年 | 15篇 |
2017年 | 17篇 |
2016年 | 29篇 |
2015年 | 36篇 |
2014年 | 51篇 |
2013年 | 63篇 |
2012年 | 77篇 |
2011年 | 63篇 |
2010年 | 42篇 |
2009年 | 31篇 |
2008年 | 49篇 |
2007年 | 42篇 |
2006年 | 51篇 |
2005年 | 35篇 |
2004年 | 43篇 |
2003年 | 36篇 |
2002年 | 47篇 |
2001年 | 7篇 |
2000年 | 10篇 |
1999年 | 10篇 |
1998年 | 8篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 4篇 |
1993年 | 7篇 |
1992年 | 5篇 |
1991年 | 2篇 |
1990年 | 4篇 |
1989年 | 5篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1985年 | 6篇 |
1984年 | 3篇 |
1983年 | 1篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 3篇 |
1976年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1971年 | 3篇 |
1969年 | 2篇 |
排序方式: 共有894条查询结果,搜索用时 484 毫秒
871.
872.
873.
R Valavaara S Pyrh?nen M Heikkinen P Rissanen G Blanco E Nordman P Taskinen L R Holsti A Hajba 《Journal of steroid biochemistry》1990,36(3):229-231
46 postmenopausal women with estrogen receptor positive breast cancer entered a phase II study with a novel antiestrogen, toremifene. Patients had either recurrent or primarily inoperable advanced disease. No prior or concurrent cytostatic or hormonal treatment was allowed. Eight patients (17%) achieved complete response (CR), 17 (37%) partial response (PR) and 13 (28%) had stabilization of their disease at least for three months. The mean durations of responses were 52 +, 53 + and 27 + weeks, respectively, with 5 patients in CR, 6 in PR and 1 with no change (NC) still continuing the treatment. No significant differences could be seen in response rates according to the concentration of estrogen receptors or presence of progesteron receptors in this group of patients. Toxicity was not a problem, in general, the treatment was well tolerated. Two side effects (sweating and vertigo) were classified as severe and one patient after achieving PR interrupted the treatment because of tremor. 相似文献
874.
Ilona Tsybulskaya Tamara Kulak Alexander Baranovsky Marina Golubeva Boleslav Kuzmitsky Elena Kalinichenko 《Bioorganic & medicinal chemistry》2013,21(17):5414-5419
The conjugates of anticancer nucleoside clofarabine [2-chloro-9-(2-deoxy-2-fluoro-β-d-arabinofuranosyl)adenine] with 1,2- and 1,3-diacylglycerophosphates have been prepared by the phosphoramidite method using a combination of 1,1,3,3-tetraisopropyldisiloxane-1,3-diyl protecting group for the sugar moiety of the nucleoside and 2-cyanoethyl protection for the phosphate fragment. Some of the synthesized conjugates exhibited cytostatic activity against HL-60, A-549, MCF-7, and HeLa tumor cell lines. 相似文献
875.
876.
Mirja Tiikkainen Marjo Tamminen Anna-Maija Häkkinen Robert Bergholm Satu Vehkavaara Juha Halavaara Kari Teramo Aila Rissanen Hannele Yki-Järvinen MD FRCP 《Obesity (Silver Spring, Md.)》2002,10(9):859-867
Objective: We determined whether fat accumulation in the liver is associated with features of insulin resistance independent of obesity. Research Methods and Procedures: We recruited 27 obese nondiabetic women in whom liver fat (LFAT) content was determined by proton spectroscopy, intra-abdominal and subcutaneous fat by magnetic resonance imaging, and insulin sensitivity by the euglycemic insulin clamp technique. The women were divided based on their median LFAT content (5%) to groups with low (3.2 ± 0.3%) and high (9.8 ± 1.5%) liver fat. The groups were almost identical with respect to age (36 ± 1 vs. 38 ± 1 years in low vs. high-LFAT), body mass index (32.2 ± 0.6 vs. 32.8 ± 0.5 kg/m2), waist-to-hip ratio, intra-abdominal, subcutaneous, and total fat content. Results: Women with high LFAT had features of insulin resistance including higher fasting serum triglyceride (1.93 ± 0.21 vs. 1.11 ± 0.09 mM, p < 0.01) and insulin (14 ± 3 vs. 10 ± 1 mU/L, p < 0.05) concentrations than women with low LFAT. The group with high LFAT also had higher 24-hour blood pressures, and lower whole-body insulin sensitivity compared with the low-LFAT group. Discussion: In obese women with previous gestational diabetes, LFAT, rather than any measure of body composition, is associated with features of insulin resistance. 相似文献
877.
878.
Emilia Komulainen Jack Badman Stephanie Rey Stuart Rulten Limei Ju Kate Fennell Ilona Kalasova Kristyna Ilievova Peter J McKinnon Hana Hanzlikova Kevin Staras Keith W Caldecott 《EMBO reports》2021,22(5)
Defects in DNA single‐strand break repair (SSBR) are linked with neurological dysfunction but the underlying mechanisms remain poorly understood. Here, we show that hyperactivity of the DNA strand break sensor protein Parp1 in mice in which the central SSBR protein Xrcc1 is conditionally deleted (Xrcc1Nes‐Cre) results in lethal seizures and shortened lifespan. Using electrophysiological recording and synaptic imaging approaches, we demonstrate that aberrant Parp1 activation triggers seizure‐like activity in Xrcc1‐defective hippocampus ex vivo and deregulated presynaptic calcium signalling in isolated hippocampal neurons in vitro. Moreover, we show that these defects are prevented by Parp1 inhibition or deletion and, in the case of Parp1 deletion, that the lifespan of Xrcc1Nes‐Cre mice is greatly extended. This is the first demonstration that lethal seizures can be triggered by aberrant Parp1 activity at unrepaired SSBs, highlighting PARP inhibition as a possible therapeutic approach in hereditary neurological disease. 相似文献
879.
880.
Aluminium has been recognized to be a neurotoxic agent and a risk factor in Alzheimer's disease and other neuronal dysfunctions. CD spectroscopic studies on two synthetic fragments of the human neurofilament protein midsized subunit (NF-M), and their alanine-for-serine-substituled and /or serine-phosphorylated derivatives showed the formation of stable, citric acid resistant complexes of Al3+with peptide ligands [M. Hollósi, Z.M. Shen, A. Perczel, and G.D. Fasman (1994) Proc. Natl. Acad. Sci. USA, vol. 9 , pp.4902-4906]. In the case of Ser-phosphorylated fragments, aβ-sheet inducing effect of Ca2+ and Al3+ ions was observed. However, the serine-containing parent peptides, NF-M 13 (KSPVPKSPVEEKG) and NF-M 17 (EEKGKSPVPKSPVEEKG), failed to show CD spectral changes reflecting β-sheet formation upon addition of Al3+ ions. On the basis of the amide I region of the Fourier transform ir spectra, in triftuoroethanol, the peptide backbone of NF-M17 and NF-M17 (A6A11) shows marked changes in the presence ofAl3+. The most significant spectral differences are seen in the car-boxyl region (> 1700 cm?l). The high-frequency component bands above 1760 cm?1 in both spectra belong to the C? O of undissociated CF3COOH. Another strong band at 1710 cm?1 which appears only in the spectrum of NF-Ml 7 (A6A11)(NF-M17 with Ser6 andSer11 replaced by Ala) can be assigned to the side chain or C-terminal COOH groups. The differential proton-ation state of the carboxyl groups in the two peptides suggests the format ion ofAl3+ complexes of different structure and stability. The Al3+ complex ofNF-Ml 7 (A6A11) is likely less stable, or one or more of the carboxylates are not coordinated to the Al3+ and thus can serve as a base to bind the liberated protons. In NF-M17 the OH groups of serines facilitate the formation of type [Al-pep(H-1)] complexes with the involvement of all carboxylategroups in the molecule. The relevance of intramolecular and intermolecular Al3+ binding to the controversial biological role of aluminium is also discussed. © 1995 John Wiley & Sons, Inc. 相似文献