全文获取类型
收费全文 | 1275篇 |
免费 | 83篇 |
出版年
2022年 | 7篇 |
2021年 | 17篇 |
2020年 | 8篇 |
2019年 | 9篇 |
2018年 | 13篇 |
2017年 | 18篇 |
2016年 | 28篇 |
2015年 | 36篇 |
2014年 | 48篇 |
2013年 | 81篇 |
2012年 | 62篇 |
2011年 | 55篇 |
2010年 | 42篇 |
2009年 | 47篇 |
2008年 | 85篇 |
2007年 | 77篇 |
2006年 | 87篇 |
2005年 | 80篇 |
2004年 | 91篇 |
2003年 | 56篇 |
2002年 | 94篇 |
2001年 | 21篇 |
2000年 | 23篇 |
1999年 | 33篇 |
1998年 | 17篇 |
1997年 | 20篇 |
1996年 | 9篇 |
1995年 | 18篇 |
1994年 | 13篇 |
1993年 | 10篇 |
1992年 | 13篇 |
1991年 | 18篇 |
1990年 | 10篇 |
1989年 | 9篇 |
1988年 | 10篇 |
1987年 | 9篇 |
1986年 | 9篇 |
1985年 | 7篇 |
1984年 | 10篇 |
1983年 | 11篇 |
1982年 | 6篇 |
1981年 | 10篇 |
1980年 | 7篇 |
1979年 | 2篇 |
1978年 | 4篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1973年 | 2篇 |
1970年 | 2篇 |
1968年 | 2篇 |
排序方式: 共有1358条查询结果,搜索用时 31 毫秒
81.
Centriolar satellites: molecular characterization, ATP-dependent movement toward centrioles and possible involvement in ciliogenesis
下载免费PDF全文
![点击此处可从《The Journal of cell biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
We identified Xenopus pericentriolar material-1 (PCM-1), which had been reported to constitute pericentriolar material, cloned its cDNA, and generated a specific pAb against this molecule. Immunolabeling revealed that PCM-1 was not a pericentriolar material protein, but a specific component of centriolar satellites, morphologically characterized as electron-dense granules, approximately 70-100 nm in diameter, scattered around centrosomes. Using a GFP fusion protein with PCM-1, we found that PCM-1-containing centriolar satellites moved along microtubules toward their minus ends, i.e., toward centrosomes, in live cells, as well as in vitro reconstituted asters. These findings defined centriolar satellites at the molecular level, and explained their pericentriolar localization. Next, to understand the relationship between centriolar satellites and centriolar replication, we examined the expression and subcellular localization of PCM-1 in ciliated epithelial cells during ciliogenesis. When ciliogenesis was induced in mouse nasal respiratory epithelial cells, PCM-1 immunofluorescence was markedly elevated at the apical cytoplasm. At the electron microscopic level, anti-PCM-1 pAb exclusively labeled fibrous granules, but not deuterosomes, both of which have been suggested to play central roles in centriolar replication in ciliogenesis. These findings suggested that centriolar satellites and fibrous granules are identical novel nonmembranous organelles containing PCM-1, which may play some important role(s) in centriolar replication. 相似文献
82.
Characterization of ZO-2 as a MAGUK family member associated with tight as well as adherens junctions with a binding affinity to occludin and alpha catenin 总被引:10,自引:0,他引:10
ZO-2, a member of the MAGUK family, was thought to be specific for tight junctions (TJs) in contrast to ZO-1, another MAGUK family member, which is localized at TJs and adherens junctions (AJs) in epithelial and nonepithelial cells, respectively. Mouse ZO-2 cDNA was isolated, and a specific polyclonal antibody was generated using corresponding synthetic peptides as antigens. Immunofluorescence microscopy with this polyclonal antibody revealed that, similarly to ZO-1, in addition to TJs in epithelial cells, ZO-2 was also concentrated at AJs in nonepithelial cells such as fibroblasts and cardiac muscle cells lacking TJs. When NH2-terminal dlg-like and COOH-terminal non-dlg-like domains of ZO-2 (N-ZO-2 and C-ZO-2, respectively) were separately introduced into cultured cells, N-ZO-2 was colocalized with endogenous ZO-1/ZO-2, i.e. at TJs in epithelial cells and at AJs in non-epithelial cells, whereas C-ZO-2 was distributed along actin filaments. Consistently, occludin as well as alpha catenin directly bound to N-ZO-2 as well as the NH2-terminal dlg-like portion of ZO-1 (N-ZO-1) in vitro. Furthermore, immunoprecipitation experiments revealed that the second PDZ domain of ZO-2 was directly associated with N-ZO-1. These findings indicated that ZO-2 forms a complex with ZO-1/occludin or ZO-1/alpha catenin to establish TJ or AJ domains, respectively. 相似文献
83.
Goro?HANYAEmail author Miki?MATSUBARA Hideki?SUGIURA Sachiko?HAYAKAWA Shunji?GOTO Toshiaki?TANAKA Joseph?SOLTIS Naohiko?NOMA 《Ecological Research》2004,19(2):179-188
The mass mortality of wild Japanese macaques (Macaca fuscata Blyth) was observed in a warm temperate forest of Yakushima, southern Japan. Demographic changes of eight troops between August 1998 and August 1999 were studied and 56% of macaques disappeared from the five intensively studied troops. Mortality varied among troops: two troops became extinct, while another troop did not decrease in size. The rate of mortality of the other troops was between 33 and 80%. The variation in mortality among the troops was either the outcome of local concentrations of mortality or of intertroop competition. The rate of mortality decreased with increasing distance from the two extinct troops and with increasing troop size; these two factors could not be separated statistically. The direct cause of death was diagnosed as pneumonia for four out of five fresh carcasses. The fleshy fruit production in autumn 1998 was the lowest in 14years, and macaques had relied on leaves earlier than in usual years. It was exceptionally hot and dry in the summer of 1998. The exceptionally poor fruit production and hot summer of this year, with the resulting shortage of high-quality foods, was consistent with the scenario that mass mortality was due to the poor nutritional conditions. However, the possibility that epidemics caused the mass mortality cannot be ruled out. Our findings proved that primates in a seemingly stable habitat experience fluctuations in demographic parameters under natural conditions. 相似文献
84.
85.
86.
Ohtaki H Dohi K Yofu S Nakamachi T Kudo Y Endo S Aruga T Goto N Watanabe J Kikuyama S Shioda S 《Regulatory peptides》2004,123(1-3):61-67
It has been reported that pituitary adenylate cyclase-activating polypeptide (PACAP) plays an important role in preventing neuronal cell death and is also a potent vasodilator. Cerebral hypotension and hypoperfusion during cerebral ischemia and neurodegenerative diseases are well known as some of the negative factors which aggravate neuronal cell death. Nevertheless, the effect of PACAP on the cerebral circulation was not understood well. Therefore, in the present study, we determined the mean arterial blood pressure (MBP), regional cerebral blood flow (rCBF) and cerebral oxygen content (pO2) in mice, and estimated the therapeutically useful doses of PACAP. Under barbiturate anesthesia, polyethylene tubes were inserted into mice to monitor MBP and to administer PACAP (5 x 10(-13)-5 x 10(-8) mol/kg) or vasoactive intestinal peptide (VIP; 5 x 10(-12) and 5 x 10(-9) mol/kg). Then, MBP, rCBF and cerebral pO2 were simultaneously measured in the mice. PACAP (5 x 10(-10)-5 x 10(-9) mol/kg) injections transiently decreased MBP, and cerebral pO2. PACAP (5 x 10(-8) mol/kg) injections produced a long-lasting potent decline of MBP, rCBF and cerebral pO2. Therefore, PACAP should be applied at low doses which do not influence the MBP and cerebral circulation to determine the therapeutically useful doses of PACAP for neuroprotection. 相似文献
87.
Galassetti P Tate D Neill RA Morrey S Wasserman DH Davis SN 《American journal of physiology. Endocrinology and metabolism》2004,287(1):E16-E24
A marked sexual dimorphism exists in healthy individuals in the pattern of blunted neuroendocrine and metabolic responses following antecedent stress. It is unknown whether significant sex-related counterregulatory differences occur during prolonged moderate exercise after antecedent hypoglycemia in type 1 diabetes mellitus (T1DM). Fourteen patients with T1DM (7 women and 7 men) were studied during 90 min of euglycemic exercise at 50% maximal O(2) consumption after two 2-h episodes of previous-day euglycemia (5.0 mmol/l) or hypoglycemia of 2.9 mmol/l. Men and women were matched for age, glycemic control, duration of diabetes, and exercise fitness and had no history or evidence of autonomic neuropathy. Exercise was performed during constant "basal" intravenous infusion of regular insulin (1 U/h) and a 20% dextrose infusion, as needed to maintain euglycemia. Plasma glucose and insulin levels were equivalent in men and women during all exercise and glucose clamp studies. Antecedent hypoglycemia produced a relatively greater (P < 0.05) reduction of glucagon, epinephrine, norepinephrine, growth hormone, and metabolic (glucose kinetics) responses in men compared with women during next-day exercise. After antecedent hypoglycemia, endogenous glucose production (EGP) was significantly reduced in men only, paralleling a reduction in the glucagon-to-insulin ratio and catecholamine responses. In conclusion, a marked sexual dimorphism exists in a wide spectrum of blunted counterregulatory responses to exercise in T1DM after prior hypoglycemia. Key neuroendocrine (glucagon, catecholamines) and metabolic (EGP) homeostatic responses were better preserved during exercise in T1DM women after antecedent hypoglycemia. Preserved counterregulatory responses during exercise in T1DM women may confer greater protection against hypoglycemia than in men with T1DM. 相似文献
88.
89.
Several compounds were found to suppress the calling behavior and in vitro pheromone biosynthesis of the Indian meal moth, Plodia interpunctella. The compounds were screened by means of a calling-behavior bioassay with female P. interpunctella. Five derivatives with activities in the nanomolar range were identified, in order of decreasing pheromonostatic activity: 4-hydroxybenzaldehyde semicarbazone (42) > 5-(4-methoxyphenyl)-1,3-oxazole (38) > 5-[4-(tert-butyl)phenyl]-1,3-oxazole (40) > 5-(3-methoxyphenyl)-1,3-oxazole (35) > 5-(4-cyanophenyl)-1,3-oxazole (36). These compounds also showed in vitro inhibitory activity in intracellular de novo pheromone biosynthesis, as determined with isolated pheromone-gland preparations that incorporated [1-(14)C]sodium acetate in the presence of the so-called pheromone-biosynthesis-activating neuropeptide (PBAN). The non-additive effect of the inhibitor with antagonist (yohimbine) for the tyramine (TA) receptor suggests that it could be a tyraminergic antagonist. Three-dimensional (3D) computer models were built from a set of compounds. Among the common-featured models generated by the program Catalyst/HipHop, aromatic-ring (AR) and H-bond-acceptor-lipophilic (HBAl) features were considered to be essential for inhibitory activity in the calling behavior and in vitro pheromone biosynthesis. Active compounds, including yohimbine, mapped well onto all the AR and HBAl features of the hypothesis. Less-active compounds were shown to be unable to achieve an energetically favorable conformation, consistent with our 3D common-feature pharmacophore models. The present hypothesis demonstrates that calling behavior and PBAN-stimulated incorporation of radioactivity are inhibited by tyraminergic antagonists. 相似文献
90.
Clathrin isoform CHC22, a component of neuromuscular and myotendinous junctions, binds sorting nexin 5 and has increased expression during myogenesis and muscle regeneration
下载免费PDF全文
![点击此处可从《Molecular biology of the cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Towler MC Gleeson PA Hoshino S Rahkila P Manalo V Ohkoshi N Ordahl C Parton RG Brodsky FM 《Molecular biology of the cell》2004,15(7):3181-3195
The muscle isoform of clathrin heavy chain, CHC22, has 85% sequence identity to the ubiquitously expressed CHC17, yet its expression pattern and function appear to be distinct from those of well-characterized clathrin-coated vesicles. In mature muscle CHC22 is preferentially concentrated at neuromuscular and myotendinous junctions, suggesting a role at sarcolemmal contacts with extracellular matrix. During myoblast differentiation, CHC22 expression is increased, initially localized with desmin and nestin and then preferentially segregated to the poles of fused myoblasts. CHC22 expression is also increased in regenerating muscle fibers with the same time course as embryonic myosin, indicating a role in muscle repair. CHC22 binds to sorting nexin 5 through a coiled-coil domain present in both partners, which is absent in CHC17 and coincides with the region on CHC17 that binds the regulatory light-chain subunit. These differential binding data suggest a mechanism for the distinct functions of CHC22 relative to CHC17 in membrane traffic during muscle development, repair, and at neuromuscular and myotendinous junctions. 相似文献