全文获取类型
收费全文 | 458篇 |
免费 | 38篇 |
专业分类
496篇 |
出版年
2023年 | 5篇 |
2022年 | 7篇 |
2021年 | 14篇 |
2020年 | 14篇 |
2019年 | 2篇 |
2018年 | 13篇 |
2017年 | 8篇 |
2016年 | 24篇 |
2015年 | 34篇 |
2014年 | 22篇 |
2013年 | 35篇 |
2012年 | 39篇 |
2011年 | 30篇 |
2010年 | 16篇 |
2009年 | 12篇 |
2008年 | 30篇 |
2007年 | 19篇 |
2006年 | 21篇 |
2005年 | 13篇 |
2004年 | 16篇 |
2003年 | 20篇 |
2002年 | 11篇 |
2001年 | 9篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1992年 | 6篇 |
1991年 | 6篇 |
1990年 | 4篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1986年 | 10篇 |
1985年 | 5篇 |
1984年 | 5篇 |
1983年 | 5篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1965年 | 2篇 |
1960年 | 1篇 |
1959年 | 2篇 |
排序方式: 共有496条查询结果,搜索用时 15 毫秒
131.
In adult moths, the cephalic aorta terminates in an apical sack from which extends a pair of optic and antennal vessels that lie on either side of the esophagus, at the dorsoanterior surface of the brain. The base of each antennal vessel is dilated to form an ampulla that contains an oval mass of tissue, the antennal ampullary gland (AAG). An ultrastructural study revealed that the AAG of the corn earworm moth, Helicoverpa zea (Lepidoptera, Noctuidae), is composed of a single type of 40-50 parenchymal cells that produce secretory granules. The secretory material is released into the lymph channel of the ampullary vessel, suggesting that the AAG is an endocrine gland. Unlike the prothoracic gland and the corpus allatum, the AAG does not receive direct neural innervation; however, portions of the aortal muscle, associated with the ampullary wall, contain neurosecretory terminals and some of their products may also affect the AAG. No morphological differences were found between the AAG of males and females, with the exception that the glands in males were slightly larger. The function of the AAG remains unknown at this time. Because the AAG is located within the ampulla of the antennal vessel, one could assume that the product(s) of this gland may influence the response of the antennal sensory neurons to external stimuli. 相似文献
132.
Effects of vitamin E on microsomal Ca(2+) -ATPase activity and calcium levels in streptozotocin-induced diabetic rat kidney 总被引:1,自引:0,他引:1
Dogru Pekiner B Daş Evcimen N Ulusu NN Bali M Karasu C 《Cell biochemistry and function》2003,21(2):177-182
Vitamin E treatment has been found to be beneficial in preventing or reducing diabetic nephropathy. Increased tissue calcium and abnormal microsomal Ca(2+)-ATPase activity have been suggested as contributing factors in the development of diabetic nephropathy. This study was undertaken to test the hypothesis that vitamin E reduces lipid peroxidation and can prevent the abnormalities in microsomal Ca(2+)-ATPase activity and calcium levels in kidney of streptozotocin (STZ)-induced diabetic rats. Male rats were rendered diabetic by a single STZ injection (55 mg x kg(-1) i.p.). After diabetes was verified, diabetic and age-matched control rats were untreated or treated with vitamin E (400-500 IU kg(-1) x day(-1), orally) for 10 weeks. Ca(2+)-ATPase activity and lipid peroxidation (MDA) were determined spectrophotometrically. Blood glucose levels increased approximately five-fold (> 500 mg x dl(-1)) in untreated-diabetic rats but decreased to 340+/-27 mg x dl(-1) in the vitamin E treated-diabetic group. Kidney MDA levels did not significantly change in the diabetic state. However, vitamin E treatment markedly inhibited MDA levels in both control and diabetic animals. Ca(2+)-ATPase activity was 0.483+/-0.008 U l(-1) in the control group and significantly increased to 0.754+/-0.010 U l(-1) in the STZ-diabetic group (p < 0.001). Vitamin E treatment completely prevented the diabetes-induced increase in Ca(2+)-ATPase activity (0.307+/-0.025 U l(-1), p < 0.001) and also reduced the enzyme activity in normal control rats. STZ-diabetes resulted in approximately two-fold increase in total calcium content of kidney. Vitamin E treatment led to a significant reduction in kidney calcium levels of both control and diabetic animals (p < 0.001). Thus, vitamin E treatment can lower blood glucose and lipid peroxidation, which in turn prevents the abnormalities in kidney calcium metabolism of diabetic rats. This study describes a potential biochemical mechanism by which vitamin E supplementation may delay or inhibit the development of cellular damage and nephropathy in diabetes. 相似文献
133.
Loading red blood cells with trehalose: a step towards biostabilization 总被引:22,自引:0,他引:22
Satpathy GR Török Z Bali R Dwyre DM Little E Walker NJ Tablin F Crowe JH Tsvetkova NM 《Cryobiology》2004,49(2):123-136
A method for freeze-drying red blood cells (RBCs) while maintaining a high degree of viability has important implications in blood transfusion and clinical medicine. The disaccharide trehalose, found in animals capable of surviving dehydration can aid in this process. As a first step toward RBC preservation, we present a method for loading RBCs with trehalose. The method is based on the thermal properties of the RBC plasma membranes and provides efficient uptake of the sugar at 37 degrees C in a time span of 7 h. The data show that RBCs can be loaded with trehalose from the extracellular medium through a combination of osmotic imbalance and the phospholipid phase transition, resulting in intracellular trehalose concentrations of about 40 mM. During the loading period, the levels of ATP and 2,3-DPG are maintained close to the levels of fresh RBCs. Increasing the membrane fluidity through the use of a benzyl alcohol results in a higher concentration of intracellular trehalose, suggesting the importance of the membrane physical state for the uptake of the sugar. Osmotic fragility data show that trehalose exerts osmotic protection on RBCs. Flow cytometry data demonstrate that incubation of RBCs in a hypertonic trehalose solution results in a fraction of cells with different complexity and that it can be removed by washing and resuspending the RBCs in an iso-osmotic medium. The data provide an important first step in long-term preservation of RBCs. 相似文献
134.
Hou X Roberts LJ Gobeil F Taber D Kanai K Abran D Brault S Checchin D Sennlaub F Lachapelle P Varma D Chemtob S 《Free radical biology & medicine》2004,36(2):163-172
F2-isoprostanes (F2-IsoP's) are biologically active prostanoids formed by free radical-mediated peroxidation of arachidonic acid. Four different F2-IsoP regioisomers (5-, 8-, 12-, and 15-series), each comprising eight racemic diastereomers, total 64 compounds. Information regarding the biological activity of IsoP's is largely limited to 15-F2t-IsoP (8-iso-PGF2alpha). We recently demonstrated that 15-F2t-IsoP and its metabolite, 2,3-dinor-5,6-dihydro-15-F2t-IsoP, evoked vasoconstriction and TXA2 generation in retina and brain microvasculature. We have now examined and compared the biological activities of a series of recently synthesized new 5-, 12-, and 15-series F2-IsoP isomers in pig retinal and brain microvasculature. We hereby show that other 15-series F2-IsoP isomers, 15-epi-15-F2t-IsoP, ent-15-F2t-IsoP, and ent-15-epi-15-F2t-IsoP, are also potent vasoconstrictors. The 12-series isomers tested, 12-F2t-IsoP and 12-epi-12-F2t-IsoP, also caused marked vasoconstriction. Of the 5-series isomers tested, 5-F2t-IsoP and 5-epi-5-F2t-IsoP possessed no vasomotor properties, whereas ent-5-F2t-IsoP caused modest vasoconstriction. The vasoconstriction of ent-5-F2t-IsoP, 12-F2t-IsoP, and 12-epi-12-F2t-IsoP was abolished by removal of the endothelium, by TXA2 synthase and receptor inhibitor (CGS12970, L670,596), and by receptor-mediated Ca2+ channel blockade (SK & F96365); correspondingly, these isomers increased TXB2 formation by activating Ca2+ influx (detected with fura 2-AM) through non-voltage-dependent receptor-mediated Ca2+ entry (SK & F96365 sensitive) in endothelial cells. In conclusion, as seen with 15-F2t-IsoP, ent-5-F2t-IsoP, 12-F2t-IsoP, and 12-epi-12-F2t-IsoP constricted both retinal and brain microvessels by inducing endothelium-dependent TXA2 synthesis. These new findings broaden the scope of our understanding regarding the potential involvement of F2-IsoP's as mediators of oxidant injury. 相似文献
135.
Modulation of pro-inflammatory gene expression by nuclear lysophosphatidic acid receptor type-1 总被引:4,自引:0,他引:4
Gobeil F Bernier SG Vazquez-Tello A Brault S Beauchamp MH Quiniou C Marrache AM Checchin D Sennlaub F Hou X Nader M Bkaily G Ribeiro-da-Silva A Goetzl EJ Chemtob S 《The Journal of biological chemistry》2003,278(40):38875-38883
Lysophosphatidic acid (LPA) is a bioactive molecule involved in inflammation, immunity, wound healing, and neoplasia. Its pleiotropic actions arise presumably by interaction with their cell surface G protein-coupled receptors. Herein, the presence of the specific nuclear lysophosphatidic acid receptor-1 (LPA1R) was revealed in unstimulated porcine cerebral microvascular endothelial cells (pCMVECs), LPA1R stably transfected HTC4 rat hepatoma cells, and rat liver tissue using complementary approaches, including radioligand binding experiments, electron- and cryomicroscopy, cell fractionation, and immunoblotting with three distinct antibodies. Coimmunoprecipitation studies in enriched plasmalemmal fractions of unstimulated pCMVEC showed that LPA1Rs are dually sequestrated in caveolin-1 and clathrin subcompartments, whereas in nuclear fractions LPA1R appeared primarily in caveolae. Immunofluorescent assays using a cell-free isolated nuclear system confirmed LPA1R and caveolin-1 co-localization. In pCMVEC, LPA-stimulated increases in cyclooxygenase-2 and inducible nitric-oxide synthase RNA and protein expression were insensitive to caveolea-disrupting agents but sensitive to LPA-generating phospholipase A2 enzyme and tyrosine kinase inhibitors. Moreover, LPA-induced increases in Ca2+ transients and/or iNOS expression in highly purified rat liver nuclei were prevented by pertussis toxin, phosphoinositide 3-kinase/Akt inhibitor wortmannin and Ca2+ chelator and channel blockers EGTA and SK&F96365, respectively. This study describes for the first time the nucleus as a potential organelle for LPA intracrine signaling in the regulation of pro-inflammatory gene expression. 相似文献
136.
Mahanty S Hutchinson K Agarwal S McRae M Rollin PE Pulendran B 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(6):2797-2801
Acute infection of humans with Ebola and Lassa viruses, two principal etiologic agents of hemorrhagic fevers, often results in a paradoxical pattern of immune responses: early infection, characterized by an outpouring of inflammatory mediators such as TNF-alpha, IL-1 beta, and IL-6, vs late stage infections, which are associated with poor immune responses. The mechanisms underlying these diverse outcomes are poorly understood. In particular, the role played by cells of the innate immune system, such as dendritic cells (DC), is not known. In this study, we show that Ebola and Lassa viruses infect human monocyte-derived DC and impair their function. Monocyte-derived DC exposed to either virus fail to secrete proinflammatory cytokines, do not up-regulate costimulatory molecules, and are poor stimulators of T cells. These data represent the first evidence for a mechanism by which Ebola and Lassa viruses target DC to impair adaptive immunity. 相似文献
137.
Agrawal S Agrawal A Doughty B Gerwitz A Blenis J Van Dyke T Pulendran B 《Journal of immunology (Baltimore, Md. : 1950)》2003,171(10):4984-4989
138.
Kontopidis G Andrews MJ McInnes C Cowan A Powers H Innes L Plater A Griffiths G Paterson D Zheleva DI Lane DP Green S Walkinshaw MD Fischer PM 《Structure (London, England : 1993)》2003,11(12):1537-1546
Inhibition of CDK2/CA (cyclin-dependent kinase 2/cyclin A complex) activity through blocking of the substrate recognition site in the cyclin A subunit has been demonstrated to be an effective method for inducing apoptosis in tumor cells. We have used the cyclin binding motif (CBM) present in the tumor suppressor proteins p21(WAF1) and p27(KIP1) as a template to optimize the minimal sequence necessary for CDK2/CA inhibition. A series of peptides were prepared, containing nonnatural amino acids, which possess nano- to micromolar CDK2-inhibitory activity. Here we present X-ray structures of the protein complex CDK2/CA, together with the cyclin groove-bound peptides H-Ala-Ala-Abu-Arg-Ser-Leu-Ile-(p-F-Phe)-NH(2) (peptide 1), H-Arg-Arg-Leu-Ile-Phe-NH(2) (peptide 2), Ac-Arg-Arg-Leu-Asn-(m-Cl-Phe)-NH(2) (peptide 3), H-Arg-Arg-Leu-Asn-(p-F-Phe)-NH(2) (peptide 4), and H-Cit-Cit-Leu-Ile-(p-F-Phe)-NH(2) (peptide 5). Some of the peptide complexes presented here were obtained through the novel technique of ligand exchange within protein crystals. This method may find general application for obtaining complex structures of proteins with surface-bound ligands. 相似文献
139.
Lipecka J Bali M Thomas A Fanen P Edelman A Fritsch J 《American journal of physiology. Cell physiology》2002,282(4):C805-C816
The ubiquitous ClC-2 Clchannel is thought to contribute to epithelial Clsecretion, but the distribution of the ClC-2 protein in human epitheliahas not been investigated. We have studied the distribution of ClC-2 inadult human and rat intestine and airways by immunoblotting andconfocal microscopy. In the rat, ClC-2 was present in the lateralmembranes of villus enterocytes and was predominant at the basolateralmembranes of luminal colon enterocytes. The expression pattern of ClC-2in the human intestine differed significantly, because ClC-2 was mainlydetected in a supranuclear compartment of colon cells. We foundsignificant expression of ClC-2 at the apex of ciliated cells in bothrat and human airways. These results show that the distribution ofClC-2 in airways is consistent with participation of ClC-2 channels inCl secretion and indicate that extrapolation of resultsfrom studies of ClC-2 function in rat intestine to human intestine isnot straightforward. 相似文献
140.
Miriam F Suzuki Márcia A Silva Daniella Murakami Maria I C C Guimaraes Kayo Okazaki 《Cellular and molecular biology, including cyto-enzymology》2002,48(5):487-492
The purpose of this study was to evaluate the degree of cytological radiation damage to peripheral blood lymphocytes induced by 153Sm-EDTMP applied for palliation of metastatic bone pain. Blood samples from 16 patients (46-82 years old), 10 without previous radiotherapy and 6 with previous radiotherapy, were collected before and one hour after the administration of a mean activity of 41.7+/-5.8 MBq/kg of 153Sm-EDTMP. Then the lymphocytes were cultured for cytokinesis block micronucleus (MN) assay. The number of MNper binucleated cells (BC) in patients without previous radiotherapy before the treatment was of 0.030 (+/- 0.016) and after one hour 0.035 (+/- 0.013), although we could find inter individual differences. The basal MN/BC of the patients with no previous radiotherapy was similar to the controls. The increment in the percentage of BC with MN was similar in patients with and without previous radiotherapy. The observed mean of MN/BC is equivalent to a dose range of 0.05 to 0.10 Gy of 153Sm-EDTMP in vitro. The relatively low frequency of lymphocyte with micronuclei after the exposure to 153Sm-EDTMP supported the contention that radiation damage in lymphocytes of patients with painful bone metastases is minimal. 相似文献