全文获取类型
收费全文 | 911篇 |
免费 | 61篇 |
专业分类
972篇 |
出版年
2023年 | 3篇 |
2022年 | 9篇 |
2021年 | 11篇 |
2019年 | 9篇 |
2018年 | 13篇 |
2017年 | 16篇 |
2016年 | 36篇 |
2015年 | 40篇 |
2014年 | 49篇 |
2013年 | 71篇 |
2012年 | 67篇 |
2011年 | 51篇 |
2010年 | 43篇 |
2009年 | 30篇 |
2008年 | 40篇 |
2007年 | 61篇 |
2006年 | 56篇 |
2005年 | 51篇 |
2004年 | 47篇 |
2003年 | 55篇 |
2002年 | 46篇 |
2001年 | 3篇 |
2000年 | 4篇 |
1999年 | 7篇 |
1998年 | 12篇 |
1997年 | 4篇 |
1996年 | 9篇 |
1995年 | 12篇 |
1994年 | 5篇 |
1993年 | 5篇 |
1992年 | 9篇 |
1991年 | 5篇 |
1990年 | 4篇 |
1989年 | 6篇 |
1987年 | 5篇 |
1986年 | 3篇 |
1985年 | 4篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1981年 | 5篇 |
1980年 | 3篇 |
1979年 | 8篇 |
1978年 | 3篇 |
1977年 | 6篇 |
1976年 | 5篇 |
1969年 | 3篇 |
1967年 | 4篇 |
1966年 | 2篇 |
1958年 | 2篇 |
1937年 | 2篇 |
排序方式: 共有972条查询结果,搜索用时 8 毫秒
61.
Di Maso V Avellini C Crocè LS Rosso N Quadrifoglio F Cesaratto L Codarin E Bedogni G Beltrami CA Tell G Tiribelli C 《Molecular medicine (Cambridge, Mass.)》2007,13(1-2):89-96
APE1/Ref-1, normally localized in the nucleus, is a regulator of the cellular response to oxidative stress. Cytoplasmic localization has been observed in several tumors and correlates with a poor prognosis. Because no data are available on liver tumors, we investigated APE1/Ref-1 subcellular localization and its correlation with survival in 47 consecutive patients undergoing hepatocellular carcinoma (HCC) resection. APE1/Ref-1 expression was determined by immunohistochemistry in HCC and surrounding liver cirrhosis (SLC) and compared with normal liver tissue. Survival probability was evaluated using Kaplan-Meier curves (log-rank test) and Cox regression. Cytoplasmic expression of APE1/Ref-1 was significantly higher in HCC than in SLC (P = 0.00001); normal liver showed only nuclear reactivity. Patients with poorly differentiated HCC showed a cytoplasmic expression three times higher than those with well-differentiated HCC (P = 0.03). Cytoplasmic localization was associated with a median survival time shorter than those with negative cytoplasmic reactivity (0.44 compared with 1.64 years, P = 0.003), and multivariable analysis confirmed that cytoplasmic APE1/Ref-1 localization is a predictor of survival. Cytoplasmic expression of APE1/Ref-1 is increased in HCC and is associated with a lower degree of differentiation and a shorter survival time, pointing to the use of the cytoplasmic localization of APE1/Ref-1 as a prognostic marker for HCC. 相似文献
62.
Bradbury A Velappan N Verzillo V Ovecka M Chasteen L Sblattero D Marzari R Lou J Siegel R Pavlik P 《Trends in biotechnology》2003,21(7):312-317
There are many ways in which the use of antibodies and antibody selection can be improved and developed for high-throughput characterization. Standard protocols, such as immunoprecipitation, western blotting and immunofluorescence, can be used with antibody fragments generated by display technologies. Together with novel approaches, such as antibody chips and intracellular immunization, these methods will yield useful proteomic data following adaptation of the protocols for increased reliability and robustness. To date, most work has focused on the use of standard, well-characterized commercial antibodies. Such protocols need to be adapted for broader use, for example, with antibody fragments or other binders generated by display technologies, because it is unlikely that traditional approaches will provide the required throughput. 相似文献
63.
Gennaro Esposito Megan Garvey Vera Alverdi Fabio Pettirossi Alessandra Corazza Federico Fogolari Maurizio Polano P. Patrizia Mangione Sofia Giorgetti Monica Stoppini Agata Rekas Vittorio Bellotti Albert J. R. Heck John A. Carver 《The Journal of biological chemistry》2013,288(24):17844-17858
The interaction at neutral pH between wild-type and a variant form (R3A) of the amyloid fibril-forming protein β2-microglobulin (β2m) and the molecular chaperone αB-crystallin was investigated by thioflavin T fluorescence, NMR spectroscopy, and mass spectrometry. Fibril formation of R3Aβ2m was potently prevented by αB-crystallin. αB-crystallin also prevented the unfolding and nonfibrillar aggregation of R3Aβ2m. From analysis of the NMR spectra collected at various R3Aβ2m to αB-crystallin molar subunit ratios, it is concluded that the structured β-sheet core and the apical loops of R3Aβ2m interact in a nonspecific manner with the αB-crystallin. Complementary information was derived from NMR diffusion coefficient measurements of wild-type β2m at a 100-fold concentration excess with respect to αB-crystallin. Mass spectrometry acquired in the native state showed that the onset of wild-type β2m oligomerization was effectively reduced by αB-crystallin. Furthermore, and most importantly, αB-crystallin reversibly dissociated β2m oligomers formed spontaneously in aged samples. These results, coupled with our previous studies, highlight the potent effectiveness of αB-crystallin in preventing β2m aggregation at the various stages of its aggregation pathway. Our findings are highly relevant to the emerging view that molecular chaperone action is intimately involved in the prevention of in vivo amyloid fibril formation. 相似文献
64.
Saskia Vanderhaegen Marcus Fislage Katarzyna Domanska Wim Versées Els Pardon Vittorio Bellotti Jan Steyaert 《Protein science : a publication of the Protein Society》2013,22(10):1349-1357
To investigate early intermediates of β2‐microglobulin (β2m) amyloidogenesis, we solved the structure of β2m containing the amyloidogenic Pro32Gly mutation by X‐ray crystallography. One nanobody (Nb24) that efficiently blocks fibril elongation was used as a chaperone to co‐crystallize the Pro32Gly β2m monomer under physiological conditions. The complex of P32G β2m with Nb24 reveals a trans peptide bond at position 32 of this amyloidogenic variant, whereas Pro32 adopts the cis conformation in the wild‐type monomer, indicating that the cis to trans isomerization at Pro32 plays a critical role in the early onset of β2m amyloid formation. 相似文献
65.
Fanciulli G Dettori A Tomasi PA Demontis MP Gianorso S Anania V Delitala G 《Life sciences》2002,71(20):2383-2390
Although it has long been known that opioid peptides cause marked changes of pituitary hormone secretion in both animals and humans, little is known about the possible effect(s) of food-derived opioids (exorphins) on pituitary function. In order to investigate the possible role of exorphins derived from wheat gluten on pituitary function, we gave the following treatments to four groups of male rats: intracerebroventricular (ICV) vehicle, Gluten Exorphin B5 (GE-B5) 200 microg ICV, naloxone intraperitoneally (IP) followed by vehicle ICV, naloxone IP followed by GE-B5 ICV. Blood samples for Prolactin (PRL) and Growth Hormone (GH) were taken at intervals for 90 minutes after vehicle or GE-B5 administration. GE-B5 strongly stimulated PRL secretion; its effect was completely abolished by naloxone administration. GH secretion was unaffected by GE-B5 under these experimental conditions. The present study shows for the first time that an opioid peptide derived from wheat gluten, GE-B5, has an effect on pituitary function when administered ICV; its mechanism of action appears to be mediated via classical opioid receptors. 相似文献
66.
The endogenous phosphorylation of human erythrocyte cytosolic proteins is markedly increased when the crude cytosol, prior to incubation in the presence of [y-32P] ATP, is submitted to DEAE-cellulose chromatography. Some proteins, including 22 and 23 kDa proteins, are preferentially phosphorylated by cytosolic casein kinase CS, whereas other proteins, including 42 kDa protein, are preferentially phosphorylated by casein kinase CTS. The CS-catalyzed phosphorylation is strongly inhibited by physiological ionic strength (150 mM KCl or NaCl) and by physiological levels (3 mM) of 2,3-bisphosphoglycerate, while CTS-catalyzed phosphorylation is unaffected. The very poor endogenous phosphorylation of these proteins in the crude cytosol may be due to the presence of other cytosolic inhibitors which are removed by DEAE-cellulose chromatography. 相似文献
67.
New types of hydrogels have been obtained starting from high bloom purified gelatin A, alone or in mixtures with hyaluronan and with a hyaluronan derivative bearing primary amino groups, by transglutaminase-catalyzed cross-linking. The reticulation process, carried out adopting two different temperature protocols, and the ensuing materials have been characterized in terms of rheologically estimated gel times, equilibrium swelling in water and in phosphate buffer solution (PBS), and rigidity modulus. Main structural and conformational factors governing the physicochemical properties and the possible application of the new hydrogels are discussed. 相似文献
68.
The direct ghrelin (Ghr) involvement in cardiovascular (CV) system homeostasis has been suggested by the expression of its receptor in CV tissues and by evidence that ghrelin mediates CV activities in animals and in humans. Moreover, low Ghr plasma levels have been reported in pathological conditions characterized by high cardiovascular risk. In the present study, we investigated Ghr effect on proliferation of human aortic endothelial cell (HAEC) and involved transduction pathways. Our results indicate that ghrelin elicited proliferation in a dose-dependent manner (EC(50) about of 5nmol/L) in cultured HAEC, and that this effect was inhibited by the receptor antagonist (D-Lys3)-GHRP-6. Western blot experiments documented an activation of external receptor activated kinases (ERK1/2) and Akt in a dose-dependent fashion, as well as involvement of the cAMP pathway in ERK1/2 phosphorylation. Experiments conducted with appropriate pharmacological inhibitors to investigate Ghr-induced HAEC proliferation confirmed the involvement of ERK1/2 and I3P/Akt pathways, as well as the role of AMP cyclase/PKA pathway in ERK1/2 phosphorylation. Our results indicate that Ghr promotes HAEC proliferation, and thus may be a protective factor against vascular damage. The low ghrelin serum levels reported in insulin-resistant states may not be able to effectively counteract endothelial cell injury. 相似文献
69.
70.
Vonasek E Mateu L Luzzati V Marquez G Vargas R Céspedes G Cotúa M Borges J 《European biophysics journal : EBJ》2001,30(1):11-16
A sural nerve dissected from a recently dead patient displayed an unusual X-ray diffraction pattern, suggesting that in situ and at the time of the patient's death the myelin sheaths were in a swollen state. Diffraction patterns of the swollen type were also recorded from: (1) a sural nerve from the corpse of a neurologically healthy person after soaking the nerve with Ringer solution at pH 5.5; (2) sciatic nerves dissected from rat cadavers at increasing time after death. In all the cases the swollen patterns reversed to the native type upon superfusion with Ringer solution at pH 7.3. The postmortem effect is to decrease the pH of the fluids surrounding the nerves in the cadavers. Our experiments show that the early postmortem processes have the effect of acidifying PNS nerves and that as a consequence of acidification the myelin sheaths swell. 相似文献