全文获取类型
收费全文 | 762篇 |
免费 | 44篇 |
出版年
2023年 | 1篇 |
2022年 | 1篇 |
2021年 | 5篇 |
2020年 | 15篇 |
2019年 | 14篇 |
2018年 | 17篇 |
2017年 | 16篇 |
2016年 | 44篇 |
2015年 | 29篇 |
2014年 | 59篇 |
2013年 | 53篇 |
2012年 | 56篇 |
2011年 | 79篇 |
2010年 | 36篇 |
2009年 | 34篇 |
2008年 | 54篇 |
2007年 | 52篇 |
2006年 | 43篇 |
2005年 | 51篇 |
2004年 | 38篇 |
2003年 | 37篇 |
2002年 | 33篇 |
2001年 | 5篇 |
2000年 | 1篇 |
1999年 | 4篇 |
1998年 | 7篇 |
1997年 | 2篇 |
1996年 | 6篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1984年 | 2篇 |
排序方式: 共有806条查询结果,搜索用时 15 毫秒
1.
MucoCept is a biotherapeutic for prevention of HIV-1 infection in women and contains a human, vaginal Lactobacillus jensenii that has been genetically enhanced to express the HIV-1 entry inhibitor, modified cyanovirin-N (mCV-N). The objective of this study was to develop a solid vaginal dosage form that supports sustained vaginal colonization of the MucoCept Lactobacillus at levels previously shown, with freshly prepared cultures, to protect macaques from SHIV infection and to test this formulation in a macaque vaginal colonization model. Vaginally disintegrating tablets were prepared by lyophilizing the formulated bacteria in tablet-shaped molds, then packaging in foil pouches with desiccant. Disintegration time, potency and stability of the tablets were assessed. For colonization, non-synchronized macaques were dosed vaginally with either one tablet or five tablets delivered over five days. Vaginal samples were obtained at three, 14, and 21 days post-dosing and cultured to determine Lactobacillus colonization levels. To confirm identity of the MucoCept Lactobacillus strain, genomic DNA was extracted from samples on days 14 and 21 and a strain-specific PCR was performed. Supernatants from bacteria were tested for the presence of the mCV-N protein by Western blot. The tablets were easy to handle, disintegrated within two minutes, potent (5.7x1011 CFU/g), and stable at 4°C and 25°C. Vaginal administration of the tablets to macaques resulted in colonization of the MucoCept Lactobacillus in 66% of macaques at 14 days post-dosing and 83% after 21 days. There was no significant difference in colonization levels for the one or five tablet dosing regimens (p=0.88 Day 14, p=0.99 Day 21). Strain-specific PCR confirmed the presence of the bacteria even in culture-negative macaques. Finally, the presence of mCV-N protein was confirmed by Western blot analysis using a specific anti-mCV-N antibody. 相似文献
2.
Taxonomic distribution and origins of the extended LHC (light-harvesting complex) antenna protein superfamily 总被引:1,自引:0,他引:1
Background
The extended light-harvesting complex (LHC) protein superfamily is a centerpiece of eukaryotic photosynthesis, comprising the LHC family and several families involved in photoprotection, like the LHC-like and the photosystem II subunit S (PSBS). The evolution of this complex superfamily has long remained elusive, partially due to previously missing families. 相似文献3.
4.
Krzysztof Kur Iwona Gabriel Joachim Morschhäuser Francesco Barchiesi Elisabetta Spreghini Sławomir Milewski 《Mycopathologia》2010,170(6):397-402
Two genes, LYS21 and LYS22, encoding isoforms of homocitrate synthase, an enzyme catalysing the first committed step in the lysine biosynthetic pathway,
were disrupted in Candida albicans using the SAT1 flipper strategy. The double null lys21Δ/lys22Δ mutant lacked homocitrate synthase activity and exhibited lysine auxotrophy in minimal media that could be fully rescued
by the addition of 0.5–0.6 mM l-lysine. On the other hand, its virulence in vivo in the model of disseminated murine candidiasis appeared identical to that
of the mother, wild-type strain. These findings strongly question a possibility of exploitation of homocitrate synthase and
possibly also other enzymes of the lysine biosynthetic pathway as targets in chemotherapy of disseminated fungal infections. 相似文献
5.
Elzbieta Sucajtys-Szulc Alicja Debska-Slizien Boleslaw Rutkowski Ryszard Milczarek Iwona Pelikant-Malecka Tomasz Sledzinski Julian Swierczynski Marek Szolkiewicz 《Molecular and cellular biochemistry》2018,439(1-2):11-18
Little is known about the effects of coffee that are not related to the presence of caffeine. The aim of the study was to analyse changes in kidney function and nucleotide metabolism related to high intake of decaffeinated coffee. Mice consumed decaffeinated coffee extract for two weeks. Activities of AMP deaminase, ecto5′-nucleotidase, adenosine deaminase, purine nucleoside phosphorylase were measured in kidney cortex and medulla by analysis of conversion of substrates into products using HPLC. Concentration of nucleotides in kidney cortex, kidney medulla and serum were estimated by HPLC. Activity of ecto5′-nucleotidase increased from 0.032 ± 0.006 to 0.049 ± 0.014 nmol/mg tissue/min in kidney cortex of mice administered high-dose decaffeinated coffee (HDC) together with increase in cortex adenosine concentration and decrease in plasma creatinine concentration. HDC leads to increased activity of ecto5′-nucleotidase in kidney cortex that translates to increase in concentration of adenosine. Surprisingly this caused improved kidney excretion function. 相似文献
6.
Iwona Popiołek Anna Niziołek Kamil Kamiński Urszula Kwolek Maria Nowakowska Krzysztof Szczubiałka 《Bioorganic & medicinal chemistry》2019,27(7):1414-1420
A cationic derivative of γ-cyclodextrin (GCD) modified with propylenediamine (PDA) was synthesized. It was shown that the derivative (GCD–PDA) is mucoadhesive and resistant to the digestion with?∝-amylase indicating that it may constitute an efficient oral delivery vehicle. GCD-PDA formed an inclusion complex with berberine (BBR), an alkaloid displaying a multitude of beneficial physiological effects. The complexed BBR penetrates a lipid membrane easier than the free one. Both uncomplexed BBR and that complexed with GCD-PDA was delivered to normal (NMuMG) and cancerous (4T1) murine mammary gland cells. In the normal cells both free and complexed BBR was homogeneously dispersed in the cytoplasm and was nontoxic up to 131?μM. In the cancerous cells uncomplexed BBR was also homogeneously dispersed but it was toxic to about 25% of cells at 131?μM, while the GCD-PDA/BBR complex was preferably localized in lysosomes and its toxicity doubled at this concentration compared to that of free BBR. Moreover, free BBR and GCD-PDA/BBR showed even more efficient inhibitory effect against murine melanoma (B16-F10) cells than against 4T1 cells. 相似文献
7.
8.
I. Rybakowska M. Szydłowska S. Szrok S. Bakuła K. Kaletha 《Nucleosides, nucleotides & nucleic acids》2015,34(3):229-234
Myasthenia gravis (MG) is characterized clinically by skeletal muscle fatigue following the excessive exercise. Interestingly most of MG patients manifest parallely also some abnormalities of the thymus.AMP-deaminase (AMPD) from human thymus was not a subject of studies up to now. In this paper, mRNA expression and some physico-chemical and immunological properties of AMPD purified from the thymus of MG patients were described. Experiments performed identified the liver isozyme (AMPD2) as the main isoform of AMPD expressed in this organ. The activity of AMPD found in this organ was higher than in other human non-(skeletal) muscle tissues indicating on role the enzyme may play in supplying of guanylates required for the intensive multiplication of thymocytes. 相似文献
9.
10.
Simon J. Watson Pinky Langat Scott M. Reid Tommy Tsan-Yuk Lam Matthew Cotten Michael Kelly Kristien Van Reeth Yu Qiu Ga?lle Simon Emilie Bonin Emanuela Foni Chiara Chiapponi Lars Larsen Charlotte Hjulsager Iwona Markowska-Daniel Kinga Urbaniak Ralf Dürrwald Michael Schlegel Anita Huovilainen Irit Davidson ádám Dán Willie Loeffen Stephanie Edwards Michel Bublot Thais Vila Jaime Maldonado Laura Valls ESNIP Consortium Ian H. Brown Oliver G. Pybus Paul Kellam 《Journal of virology》2015,89(19):9920-9931