全文获取类型
收费全文 | 1100篇 |
免费 | 63篇 |
出版年
2023年 | 2篇 |
2022年 | 16篇 |
2021年 | 28篇 |
2020年 | 9篇 |
2019年 | 21篇 |
2018年 | 14篇 |
2017年 | 21篇 |
2016年 | 25篇 |
2015年 | 54篇 |
2014年 | 57篇 |
2013年 | 74篇 |
2012年 | 77篇 |
2011年 | 103篇 |
2010年 | 56篇 |
2009年 | 43篇 |
2008年 | 67篇 |
2007年 | 79篇 |
2006年 | 55篇 |
2005年 | 61篇 |
2004年 | 59篇 |
2003年 | 44篇 |
2002年 | 47篇 |
2001年 | 11篇 |
2000年 | 9篇 |
1999年 | 14篇 |
1998年 | 9篇 |
1997年 | 11篇 |
1996年 | 5篇 |
1995年 | 2篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1992年 | 12篇 |
1991年 | 8篇 |
1990年 | 6篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1985年 | 3篇 |
1983年 | 4篇 |
1982年 | 6篇 |
1981年 | 2篇 |
1979年 | 4篇 |
1977年 | 2篇 |
1973年 | 4篇 |
1972年 | 5篇 |
1970年 | 2篇 |
1969年 | 2篇 |
1968年 | 2篇 |
1967年 | 5篇 |
1966年 | 3篇 |
1965年 | 3篇 |
排序方式: 共有1163条查询结果,搜索用时 31 毫秒
71.
Schwabe TM Gloddek K Schluesener D Kruip J 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2003,786(1-2):45-59
The gene products Ycf3 (hypothetical chloroplast open reading frame) and BtpA (biogenesis of thylakoid protein) are thought to be involved in the biogenesis of the membrane protein complex photosystem I (PSI) from Synechocystis PCC 6803. PSI consists of 12 different subunits and binds more than 100 cofactors, making it a model protein to study different aspects of membrane protein biogenesis. For a detailed biophysical characterization of Ycf3 and BtpA pure proteins must be available in sufficient quantities. Therefore we cloned the corresponding genes into expression vectors. To facilitate purification we created His-tagged versions of Ycf3 and BtpA in addition to the unmodified forms. Immobilized metal affinity chromatography (IMAC) yielded His-tagged proteins which were used for the production of antibodies. Purification strategies for non-tagged proteins could also be established: Ycf3 could be purified in soluble form using a two-step purification in which ammonium sulfate precipitation was combined with anion-exchange chromatography (IEC). BtpA had to be purified from inclusion bodies by two-consecutive IEC steps under denaturing conditions. An optimized refolding protocol was established that yielded pure BtpA. In all cases, MALDI-TOF peptide mass fingerprinting (PMF) was used to confirm protein identity. Initially, size exclusion chromatography and CD-spectroscopy were used for biophysical characterization of the proteins. Both Ycf3 and BtpA show homo-oligomerization in vitro. In summary, purification protocols for Ycf3 and BtpA have been designed that yield pure proteins which can be used to probe the molecular function of these proteins for membrane protein biogenesis. 相似文献
72.
73.
The zebrafish van gogh mutation disrupts tbx1, which is involved in the DiGeorge deletion syndrome in humans 总被引:6,自引:0,他引:6
Piotrowski T Ahn DG Schilling TF Nair S Ruvinsky I Geisler R Rauch GJ Haffter P Zon LI Zhou Y Foott H Dawid IB Ho RK 《Development (Cambridge, England)》2003,130(20):5043-5052
The van gogh (vgo) mutant in zebrafish is characterized by defects in the ear, pharyngeal arches and associated structures such as the thymus. We show that vgo is caused by a mutation in tbx1, a member of the large family of T-box genes. tbx1 has been recently suggested to be a major contributor to the cardiovascular defects in DiGeorge deletion syndrome (DGS) in humans, a syndrome in which several neural crest derivatives are affected in the pharyngeal arches. Using cell transplantation studies, we demonstrate that vgo/tbx1 acts cell autonomously in the pharyngeal mesendoderm and influences the development of neural crest-derived cartilages secondarily. Furthermore, we provide evidence for regulatory interactions between vgo/tbx1 and edn1 and hand2, genes that are implicated in the control of pharyngeal arch development and in the etiology of DGS. 相似文献
74.
Mroczko B Szmitkowski M Okulczyk B Piotrowski Z 《Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society》2001,39(Z2):110-111
Granulocyte-macrophage-colony stimulating factor (GM-CSF) belongs to the group of glycoproteins called colony-stimulating factors (CSFs). It has been shown that the activity of CSFs is not limited to the hematopoietic cells but can also affect the proliferation of colon carcinoma cell lines. The purpose of this investigation was to compare the serum level of GM-CSF in colorectal cancer patients to a control group, to assess the level of GM-CSF in relation to the level of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9), and to define the sensitivity, the specificity and the predictive values of GM-CSF in colorectal cancer. In this study, the serum level of tumour markers was measured in 30 patients with colorectal cancer and in 20 healthy subjects. GM-CSF was assayed using ELISA system, CEA and CA 19-9 were measured by MEIA. The serum levels of CEA, CA 19-9 and GM-CSF were higher in the patients with colorectal cancer than in the control group. The sensitivities of CEA (63%) and CA 19-9 (56%) were lower than the GM-CSF sensitivity (80%). The specificities of tumour markers were 70% (CEA, GM-CSF) and 75% for CA 19-9. The GM-CSF predictive v values were higher than the CEA and CA 19-9 values. These results suggest that GM-CSF may be useful as tumour marker in colorectal cancer, but further studies are needed. 相似文献
75.
Electron transport system (ETS) activity was measured in Chirocephalus croaticus from the intermittent lake, Petelinjsko Jezero. The ETS activities were measured at 5, 10, 15, 20, and 25 °C, and were studied separately in juveniles, females and males. Juveniles had significantly higher activity than adults at a standard temperature of 20 °C. The mass-specific ETS activity decreased with increasing size of the animals; the value b was 0.787. Respiration rates (R) were determined at 20 °C and the ratio ETS/R (±standard deviation) for C. croaticus was 1.43±0.46 (n=38). ETS activity increased with temperature. Females had higher Q10 than males in higher temperature range (t-test; t=2.50; d.f.=8; p<0.05). Activation energy Ea was higher for females than males (t-test; t=2.35; d.f.=8; p<0.05). Females exhibited lower ETS activity than males over the lower temperature range, but their ETS could function more efficient at higher temperature. 相似文献
76.
Suppression of endothelin-converting enzyme-1 during buccal mucosal ulcer healing: effect of chronic alcohol ingestion 总被引:3,自引:0,他引:3
Slomiany BL Piotrowski J Slomiany A 《Biochemical and biophysical research communications》2000,271(2):318-322
Among the factors affecting the efficiency of soft oral tissue healing is endothelin-1 (ET-1), a potent vasoactive peptide produced from a biologically inactive big ET-1 by the action of endothelin-converting enzyme-1 (ECE-1). We investigated the expression of ECE-1 during buccal mucosal ulcer healing in rats maintained for 5 weeks on alcohol containing or control diet. The mucosal activity of ECE-1, characterized by sensitivity to phosphoramidon, was associated with microsomal fraction and showed an elevated (3.1-fold) level in the alcohol diet group. Moreover, the ulcer onset in the alcohol group was reflected in a 39% greater expression of ECE-1 activity, and was accompanied by a 1.4-fold greater increase in TNF-alpha and a 2.5-fold greater enhancement in epithelial cell apoptosis. While in both groups the ulcer healing was associated with a decrease in buccal mucosal expression of ECE-1, as well as a decline in TNF-alpha and apoptosis, the changes were significantly slower in the alcohol diet group and manifested by a 40% delay in healing. Thus, chronic alcohol ingestion leads to up-regulation of ECE-1 expression, induction of TNF-alpha, and triggering apoptotic events that delay the mucosal repair. 相似文献
77.
Role of basic fibroblast growth factor in the suppression of apoptotic caspase-3 during chronic gastric ulcer healing. 总被引:1,自引:0,他引:1
BACKGROUND: In the course of ulcer healing an array of factors compel mucosal cells to proliferate, differentiate, and migrate to the site of injury. The recognition of triggering cues requires close interaction between the regulatory proteins integrating the growth factor and cytokine- mediated signals that propel cells through the cycle events, or to signal apoptosis. In this study, we analyzed the interplay between mucosal expression of the receptor-bound basic fibroblast growth factor (bFGF-R) and cyclin-dependent kinase (Cdk2), and the activity of apoptotic protease, caspase-3, and constitutive nitric oxide synthase (cNOS) during chronic gastric ulcer healing. METHODS: The experiments were conducted with gastric mucosa of rats at different stages of acetic acid-induced chronic gastric ulcer healing. RESULTS: The ulcer onset (2 days following injury) was characterized by a massive epithelial apoptosis associated with a 33-fold increase in caspase-3 activity and a 7.6-fold drop in cNOS, while the mucosal expression of Cdk2 fell by an 18% and that of bFGF-R by 12%. The ulcer healing was accompanied by a rapid elevation in bFGF-R and Cdk2, and a slow recovery in cNOS activity, while the caspase-3 activity and epithelial apoptosis showed a marked decline. The bFGF-R and Cdk2 reached their maximums of 2.2-2.3-fold at 4-6 day of healing, while the caspase-3 activity and the apoptotic DNA fragmentation showed a 3-fold decline by the 7th day of healing. However, the activity of cNOS remained about 50% lower than that of the controls. CONCLUSIONS: Taken together, these results provide strong indications that the initial phase of ulcer healing involves the inhibition of apoptotic caspase activities by a signaling events initiated by bFGF-receptor activation and propagated by the regulatory kinases that propel the cell cycle progression. Our findings also point towards participation of cNOS in the suppression of proapoptotic activities in gastric mucosa. 相似文献
78.
Antimicrobial and Cytotoxic Activity of Extracts of Ferula heuffelii Griseb. ex Heuff. and Its Metabolites
下载免费PDF全文
![点击此处可从《化学与生物多样性》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Ivan Pavlović Silvana Petrović Marina Milenković Tatjana Stanojković Dejan Nikolić Aleksej Krunić Marjan Niketić 《化学与生物多样性》2015,12(10):1585-1594
The antimicrobial and cytotoxic activities of isolates (CHCl3 and MeOH extracts and selected metabolites) obtained from the underground parts of the Balkan endemic plant Ferula heuffelii Griseb . ex Heuff . were assessed. The CHCl3 and MeOH extracts exhibited moderate antimicrobial activity, being more pronounced against Gram‐positive than Gram‐negative bacteria, especially against Staphylococcus aureus (MIC=12.5 μg/ml for both extracts) and Micrococcus luteus (MIC=50 and 12.5 μg/ml, resp.). Among the tested metabolites, (6E)‐1‐(2,4‐dihydroxyphenyl)‐3,7,11‐trimethyl‐3‐vinyldodeca‐6,10‐dien‐1‐one ( 2 ) and (2S*,3R*)‐2‐[(3E)‐4,8‐dimethylnona‐3,7‐dien‐1‐yl]‐2,3‐dihydro‐7‐hydroxy‐2,3‐dimethylfuro[3,2‐c]coumarin ( 4 ) demonstrated the best antimicrobial activity. Compounds 2 and 4 both strongly inhibited the growth of M. luteus (MIC=11.2 and 5.2 μM , resp.) and Staphylococcus epidermidis (MIC=22.5 and 10.5 μM , resp.) and compound 2 additionally also the growth of Bacillus subtilis (MIC=11.2 μM ). The cytotoxic activity of the isolates was tested against three human cancer cell lines, viz., cervical adenocarcinoma (HeLa), chronic myelogenous leukemia (K562), and breast cancer (MCF‐7) cells. The CHCl3 extract exhibited strong cytotoxic activity against all cell lines (IC50<11.0 μg/ml). All compounds strongly inhibited the growth of the K562 and HeLa cell lines. Compound 4 exhibited also a strong activity against the MCF‐7 cell line, comparable to that of cisplatin (IC50=22.32±1.32 vs. 18.67±0.75μM ). 相似文献
79.
Indrikis Krams Sanita Kecko Katariina Kangassalo Fhionna R. Moore Eriks Jankevics Inna Inashkina Tatjana Krama Vilnis Lietuvietis Laila Meija Markus J. Rantala 《Insect Science》2015,22(3):431-439
The resources available to an individual in any given environment are finite, and variation in life history traits reflect differential allocation of these resources to competing life functions. Nutritional quality of food is of particular importance in these life history decisions. In this study, we tested trade‐offs among growth, immunity and survival in 3 groups of greater wax moth (Galleria mellonella) larvae fed on diets of high and average nutritional quality. We found rapid growth and weak immunity (as measured by encapsulation response) in the larvae of the high‐energy food group. It took longer to develop on food of average nutritional quality. However, encapsulation response was stronger in this group. The larvae grew longer in the low‐energy food group, and had the strongest encapsulation response. We observed the highest survival rates in larvae of the low‐energy food group, while the highest mortality rates were observed in the high‐energy food group. A significant negative correlation between body mass and the strength of encapsulation response was found only in the high‐energy food group revealing significant competition between growth and immunity only at the highest rates of growth. The results of this study help to establish relationships between types of food, its nutritional value and life history traits of G. mellonella larvae. 相似文献
80.
Marko Dragas Igor Koncar Dragan Opacic Nikola Ilic Zivan Maksimovic Miroslav Markovic Marko Ercegovac Tatjana Simic Marija Pljesa-Ercegovac Lazar Davidovic 《PloS one》2015,10(4)