全文获取类型
收费全文 | 1544篇 |
免费 | 94篇 |
专业分类
1638篇 |
出版年
2022年 | 11篇 |
2021年 | 15篇 |
2019年 | 10篇 |
2018年 | 11篇 |
2016年 | 19篇 |
2015年 | 44篇 |
2014年 | 41篇 |
2013年 | 85篇 |
2012年 | 56篇 |
2011年 | 51篇 |
2010年 | 50篇 |
2009年 | 28篇 |
2008年 | 80篇 |
2007年 | 56篇 |
2006年 | 66篇 |
2005年 | 66篇 |
2004年 | 73篇 |
2003年 | 52篇 |
2002年 | 65篇 |
2001年 | 60篇 |
2000年 | 52篇 |
1999年 | 48篇 |
1998年 | 14篇 |
1997年 | 18篇 |
1996年 | 10篇 |
1995年 | 17篇 |
1994年 | 13篇 |
1993年 | 16篇 |
1992年 | 47篇 |
1991年 | 42篇 |
1990年 | 40篇 |
1989年 | 38篇 |
1988年 | 26篇 |
1987年 | 24篇 |
1986年 | 21篇 |
1985年 | 25篇 |
1984年 | 23篇 |
1983年 | 24篇 |
1982年 | 12篇 |
1981年 | 11篇 |
1980年 | 19篇 |
1979年 | 21篇 |
1978年 | 11篇 |
1977年 | 12篇 |
1976年 | 10篇 |
1975年 | 13篇 |
1974年 | 10篇 |
1973年 | 14篇 |
1972年 | 10篇 |
1969年 | 8篇 |
排序方式: 共有1638条查询结果,搜索用时 15 毫秒
51.
Whole-plant development trajectories and sapling leaf displays were compared for two sympatric congeneric species, Pterospermum diversifolium and P. javanicum, in a tropical floodplain forest in East Kalimantan, Indonesia. We assessed their growth strategies and developed hypotheses for their coexistence within the community. Pterospermum diversifolium retains a monoaxial growth habit that promotes quick stem elongation; thus, it is taller when branches are initiated than is P. javanicum. The species differed significantly in height growth and total crown expansion per unit increment of biomass: monoaxial P. diversifolium saplings devote more effort to stem elongation, whereas branched P. javanicum saplings devote more effort to branch expansion. Monoaxial P. diversifolium sustained more severe self-shading than P. javanicum. The sapling growth strategy of P. diversifolium appears to be dynamic, emphasizing the opportunistic use of light following a disturbance, whereas that of P. javanicum appears to be static, optimizing leaf display for current light conditions. The advantages of these strategies depend on context, and the two species may coexist within a community by adopting different regeneration niches based on differing understory light conditions: P. diversifolium is favored over P. javanicum at high light levels, but the opposite is true at low light levels. 相似文献
52.
Takahashi H Soma S Muramatsu M Oka M Fukuchi Y 《American journal of physiology. Lung cellular and molecular physiology》2001,280(6):L1104-L1114
Pulmonary veins show greater sensitivity to endothelin (ET)-1-induced vasoconstriction than pulmonary arteries, and remodeling was observed in pulmonary veins under hypoxic conditions. We examined, using an immunohistochemical method, the expression of Big ET-1, ET-converting enzyme (ECE), and ET(A) and ET(B) receptors in rat pulmonary veins under normoxic and hypoxic conditions. In control rats, Big ET-1 and ECE were coexpressed in the intima and media of the pulmonary veins, with an even distribution along the axial pathway. ET(A) and ET(B) receptors were expressed in the pulmonary veins, with a predominant distribution in the proximal segments. The expression of Big ET-1 was more abundant in the pulmonary veins than in the pulmonary arteries. After exposure to hypoxia for 7 or 14 days, the expression of Big ET-1, ECE, and ET receptors increased in small pulmonary veins. Increases in the medial thickness, wall thickness, and immunoreactivity for alpha-smooth muscle actin were also observed in the small pulmonary veins under hypoxic conditions. The upregulation of ET-1 and ET receptors in the small pulmonary veins is associated with vascular remodeling, which may lead to the development of hypoxic pulmonary hypertension. 相似文献
53.
Dukgyu Lee Tatsujiro Oka Beth Hunter Alison Robinson Sylvia Papp Kimitoshi Nakamura Wattamon Srisakuldee Barbara E. Nickel Peter E. Light Jason R. B. Dyck Gary D. Lopaschuk Elissavet Kardami Michal Opas Marek Michalak 《PloS one》2013,8(2)
Background
Calreticulin, a Ca2+-buffering chaperone of the endoplasmic reticulum, is highly expressed in the embryonic heart and is essential for cardiac development. After birth, the calreticulin gene is sharply down regulated in the heart, and thus, adult hearts have negligible levels of calreticulin. In this study we tested the role of calreticulin in the adult heart.Methodology/Principal Findings
We generated an inducible transgenic mouse in which calreticulin is targeted to the cardiac tissue using a Cre/loxP system and can be up-regulated in adult hearts. Echocardiography analysis of hearts from transgenic mice expressing calreticulin revealed impaired left ventricular systolic and diastolic function and impaired mitral valve function. There was altered expression of Ca2+ signaling molecules and the gap junction proteins, Connexin 43 and 45. Sarcoplasmic reticulum associated Ca2+-handling proteins (including the cardiac ryanodine receptor, sarco/endoplasmic reticulum Ca2+-ATPase, and cardiac calsequestrin) were down-regulated in the transgenic hearts with increased expression of calreticulin.Conclusions/Significance
We show that in adult heart, up-regulated expression of calreticulin induces cardiomyopathy in vivo leading to heart failure. This is due to an alternation in changes in a subset of Ca2+ handling genes, gap junction components and left ventricle remodeling. 相似文献54.
Kanouchi H Matsumoto M Taga M Yamada K Oka T Toné S Minatogawa Y 《Protein science : a publication of the Protein Society》2005,14(9):2344-2349
Perchloric acid-soluble protein (PSP) is highly conserved during evolution from bacteria to mammals. Although PSP has been recognized as an inhibitor of translation and proliferation in vitro, its precise biological role has not yet been elucidated. Since we previously found similar distributions for PSP and the endoplasmic reticulum (ER) and Golgi complex, the intracellular distribution of PSP was analyzed in more detail. Immunofluorescence studies indicated that PSP co-localized with the ER and Golgi complex, since the distribution pattern of PSP was well matched to both of these organelles. An immunoelectron microscopic study revealed PSP was located not only in the cytosol but also on the surface of the outer ER membrane. Since PSP was present on the ER, we speculated that it may be associated with ER function. Therefore, we analyzed whether or not the ER stress response, which is one of the ER functions, affected PSP expression. The results showed that various ER stressors (thapsigargin, A23187, tunicamycin, brefeldin A, and cisplatin) provoked a dramatic change in the localization of PSP from outside of the nucleus to inside the nucleus within 3 h. Moreover, the ER stressors induced PSP expression. These results suggest that PSP is involved in the cellular response to ER stressors, and that the change in localization of PSP from the ER to the nucleus may be associated with ER stress responses. 相似文献
55.
Hitoshi Kumagai Yoshimi Oka Motoko Akita-TanakaKatsuya Inoue 《Inorganica chimica acta》2002,332(1):176-180
The hydrothermal synthesis, single crystal X-ray structure and magnetic properties of a two-dimensional (2-D) coordination polymer, [Ni4(C6(COO)6)(OH)2(H2O)6] (1), is described. Complex 1 consists of dimer motifs of pseudo octahedral NiO6 linked through μ3-OH to generate one-dimensional (1-D) chains which are further bridged by the mellitate ligands to form non interpenetrated undulating sheet structure. The sheets are further connected by hydrogen bonding interaction to yield a three-dimensional (3-D) structure. The temperature dependence of magnetic susceptibilities revealed the presence of antiferromagnetic interaction between nickel centers. 相似文献
56.
Imai J Katagiri H Yamada T Ishigaki Y Ogihara T Uno K Hasegawa Y Gao J Ishihara H Sasano H Oka Y 《Obesity (Silver Spring, Md.)》2006,14(7):1132-1141
Objective: Several lines of evidence suggest important roles for adiponectin in glucose and lipid metabolism and atherosclerosis. However, the mechanisms regulating serum adiponectin levels and adiponectin production are still not completely understood. Our aim was to determine whether adiponectin synthesis is physiologically regulated by the sympathetic nervous system (SNS). Research Methods and Procedures: Mice were exposed to cold (4 °C) for 12 hours and for 24 hours with or without inhibition of noradrenaline synthesis or pan‐β adrenergic function, followed by measurement of serum adiponectin concentrations and levels of adiponectin and uncoupling protein (UCP) 1 expressions in various white adipose tissues (WATs). Results: Cold exposure significantly reduced serum adiponectin concentrations without changing body weights or WAT sizes in either subcutaneous or intra‐abdominal fat tissues. The serum adiponectin reduction was associated with a decrease in adiponectin mRNA expression in subcutaneous, epididymal, and mesenteric fat tissues. In these adipose tissues, UCP1 expression was markedly enhanced, suggesting SNS activation in these tissues. Administration of α‐methyl‐p‐tyrosine or a combination of SR59230A and propranolol reversed the cold‐exposure‐induced decreases in serum adiponectin concentrations and adiponectin mRNA expression in these tissues. In contrast, in retroperitoneal fat, the effects of cold exposure on adiponectin and UCP1 expressions were strikingly weak but were not reversed by SNS inhibitors. Discussion: SNS physiologically regulates serum adiponectin levels and adiponectin synthesis in WATs in vivo, although responsiveness to SNS stimulation differs markedly among WATs. Sympathetic activation might be involved in development of the metabolic syndrome by modulation of serum adiponectin concentrations. 相似文献
57.
Takahashi R Ishihara H Tamura A Yamaguchi S Yamada T Takei D Katagiri H Endou H Oka Y 《American journal of physiology. Endocrinology and metabolism》2006,290(2):E308-E316
Abnormal glucagon secretion is often associated with diabetes mellitus. However, the mechanisms by which nutrients modulate glucagon secretion remain poorly understood. Paracrine modulation by beta- or delta-cells is among the postulated mechanisms. Herein we present further evidence of the paracrine mechanism. First, to activate cellular metabolism and thus hormone secretion in response to specific secretagogues, we engineered insulinoma INS-1E cells using an adenovirus-mediated expression system. Expression of the Na+-dependent dicarboxylate transporter (NaDC)-1 resulted in 2.5- to 4.6-fold (P < 0.01) increases in insulin secretion in response to various tricarboxylic acid cycle intermediates. Similarly, expression of glycerol kinase (GlyK) increased insulin secretion 3.8- or 4.2-fold (P < 0.01) in response to glycerol or dihydroxyacetone, respectively. This cell engineering method was then modified, using the Cre-loxP switching system, to activate beta-cells and non-beta-cells separately in rat islets. NaDC-1 expression only in non-beta-cells, among which alpha-cells are predominant, caused an increase (by 1.8-fold, P < 0.05) in glucagon secretion in response to malate or succinate. However, the increase in glucagon release was prevented when NaDC-1 was expressed in whole islets, i.e., both beta-cells and non-beta-cells. Similarly, an increase in glucagon release with glycerol was observed when GlyK was expressed only in non-beta-cells but not when it was expressed in whole islets. Furthermore, dicarboxylates suppressed basal glucagon secretion by 30% (P < 0.05) when NaDC-1 was expressed only in beta-cells. These data demonstrate that glucagon secretion from rat alpha-cells depends on beta-cell activation and provide insights into the coordinated mechanisms underlying hormone secretion from pancreatic islets. 相似文献
58.
59.
Prolactin induces MFG-E8 production in macrophages via transcription factor C/EBPβ-dependent pathway
Aziz MM Ishihara S Rumi MA Mishima Y Oshima N Kadota C Moriyama I Li YY Rahman FB Otani A Oka A Ishimura N Kadowaki Y Amano Y Kinoshita Y 《Apoptosis : an international journal on programmed cell death》2008,13(5):609-620
The lactogenic hormone prolactin (PRL) regulates milk protein gene expression in mammary glands. To maintain homeostatic balance
in the body, milk fat globule epidermal growth factor 8 (MFG-E8) is vital for phagocytic clearance of apoptotic cells. We
investigated the effects of PRL on MFG-E8 expression in macrophages by evaluating its promoter function. Macrophages were
stimulated with PRL, and the expression of MFG-E8 was determined using real-time PCR and Western blotting. The role of MFG-E8
on phagocytosis of apoptotic cells in PRL-treated macrophages was assessed using microscopy, while the response of PRL to
MFG-E8 expression was evaluated using luciferase assay. Following treatment with PRL, significant up-regulations of the PRL
receptor and MFG-E8 were observed in macrophages, though PRL-treated macrophages more efficiently engulfed apoptotic cells.
The results of MFG-E8 promoter analysis showed considerable up-regulation of promoter activity in macrophages following PRL
treatment and results from mutation analysis of the MFG-E8 promoter suggested that the C/EBPβ binding site was responsible
for PRL-induced activation of the MFG-E8 promoter. C/EBPβ activity was found to be up-regulated in PRL-treated cells as revealed
by an electrophoretic mobility shift assay (EMSA). In conclusion, PRL is a potent inducer of MFG-E8 expression in macrophages,
while its effect is mediated by the presence of a responsive element in the MFG-E8 promoter. 相似文献
60.