全文获取类型
收费全文 | 2554篇 |
免费 | 127篇 |
国内免费 | 1篇 |
专业分类
2682篇 |
出版年
2022年 | 13篇 |
2021年 | 19篇 |
2020年 | 10篇 |
2019年 | 23篇 |
2018年 | 24篇 |
2017年 | 20篇 |
2016年 | 39篇 |
2015年 | 63篇 |
2014年 | 84篇 |
2013年 | 212篇 |
2012年 | 144篇 |
2011年 | 171篇 |
2010年 | 111篇 |
2009年 | 107篇 |
2008年 | 178篇 |
2007年 | 147篇 |
2006年 | 140篇 |
2005年 | 146篇 |
2004年 | 136篇 |
2003年 | 152篇 |
2002年 | 138篇 |
2001年 | 32篇 |
2000年 | 32篇 |
1999年 | 51篇 |
1998年 | 37篇 |
1997年 | 42篇 |
1996年 | 32篇 |
1995年 | 26篇 |
1994年 | 17篇 |
1993年 | 31篇 |
1992年 | 31篇 |
1991年 | 24篇 |
1990年 | 11篇 |
1989年 | 17篇 |
1988年 | 11篇 |
1987年 | 20篇 |
1986年 | 11篇 |
1985年 | 15篇 |
1984年 | 17篇 |
1983年 | 22篇 |
1982年 | 14篇 |
1981年 | 12篇 |
1980年 | 14篇 |
1978年 | 9篇 |
1977年 | 9篇 |
1976年 | 9篇 |
1975年 | 10篇 |
1973年 | 5篇 |
1971年 | 5篇 |
1970年 | 6篇 |
排序方式: 共有2682条查询结果,搜索用时 15 毫秒
81.
C-Glucosidic ellagitannin dimers were classified as types A-C according to a putative biogenetic oligomerization mode. They were characterized by different positions of the C-C bond between the phenolic acyl unit in one monomer and the benzylic C-1 of the open-chain glucose core in the other monomer. In recent years, four C-glucosidic tannins, melasquanins A-D (18-21), have been found in the leaves of Melaleuca squarrosa Donn ex Sm. (Myrtaceae). These are characterized as a dimer (melasquanin A) of a dimerization mode (type D), and trimers (melasquanins B-D) based on spectroscopic analysis including various two-dimensional nuclear magnetic resonance (2D NMR) experiments. Melasquanins B (19) and D (21) are C-glucosidic tannin trimers with a structure containing, non-repeating condensation modes, which was hitherto unknown. 相似文献
82.
Hisakazu Mihara Kin-Ya Tomizaki Norikazu Nishino Tsutomu Fujimoto Haruhiko Tamaoki Yuji Kobayashi 《Biopolymers》1994,34(7):963-967
A model 16-peptide of endothelin-1 (MET-1), which has the minimized sequence homology to the corresponding pan of endothelin-1 (ET-1), was designed to confirm the cystine-stabilized α-helix motif. The model structure consists of an extended structure, a β-turn part, and an α-helix structure that is stabilized by two disulfide bonds. The α-helix segment was designed to emphasize the amphiphilic nature. In order to combine the extended structure and the α-helix segment, a D -Ala-Pro sequence was selected to fix the β-turn. The model endothelin 16-peptide amide was synthesized by solid-phase synthesis on a 4-methylbenzhydrylamine resin. Its conformation was examined by CD and two-dimensional (2D) 1H-nmr measurements. MET-1 showed similar CD patterns to ET-1 in both buffer and 50% aqueous trifluoroethanol solution. The 2D nmr experiments in 50% aqueous ethylene glycol revealed that MET-1 closely resembles the conformation of ET-1 with an extended structure, an α-helix, and a β-turn unit in the same position of the sequence. Furthermore, model peptides without disulfide bond(s) could not assume a stable structure in aqueous solution, while they did have similar α-helical content in 50% trifluoroethanol with MET-1. When the two disulfide bridges were simultaneously formed, the peptide with the correct disulfide bonds (MET-1) was obtained in threefold excess to the isomer (apamin type. MET-2). These findings obtained by the modeling of ET-1 showed an important role for the stabilization of peptide conformation with disulfide bonds. © 1994 John Wiley & Sons, Inc. 相似文献
83.
Yuzuru Hamada Toshifumi Udono Migaku Teramoto Tsutomu Sugawara 《Primates; journal of primatology》1996,37(3):279-295
Growth of chimpanzees reared at the Kumamoto Primates Park of Sanwa Kagaku Kenkyusho Co. Ltd. was studied cross-sectionally
from the viewpoints of somatic growth and reproductive maturation. Distance and velocity curves were expressed using spline
function method. Males showed adolescent growth acceleration in body weight, with a peak at 7.86 yrs of age, but not in trunk
length. Females showed continuous rapid growth from mid-juvenile to adolescent phase in both body weight and trunk length,
but no isolated adolescent spurt. The Sanwa chimpanzees matured at about 12.5 yrs of age for females and 15.0 yrs for males.
The mean adult weights and trunk lengths were 53.2 kg and 507.8 mm for males and 42.7 kg and 481.6 mm for females. The Sanwa
chimpanzees had similar growth patterns to those of the Yerkes chimpanzees, although they showed a slight delay in infancy,
and a higher growth rate from the early juvenile phase onwards. Growth patterns in these two laboratories may be regarded
as “normative” for laboratory-reared chimpanzees. They matured earlier than wild chimpanzees by more than two years. The major
reason for the retarded maturation in wild chimpanzees is the delay of growth from infant to the early juvenile phases (0–4
yrs of age), probably owing to a limited nutritional supply from the mother. Development of the testes comprised three phases:
slow growth from infant to juvenile (until 6.4 yrs); rapid growth around adolescence (until 9.2 yrs); and adult (mean testicular
volume, 187 cm3). Setting the nutritional standard at 2,000–2,600 Cal/day (= Kcal/day) per adult, calories were considered for captive chimpanzees
in each age class. 相似文献
84.
To prepare an immobilized protease with a high activity for transesterification of vinyl n-butyrate with 3-methyl-1-butanol (isoamyl alcohol) in organic media, a protease was entrapped into organic–inorganic hybrid silica gel on Celite 545 by the sol-gel method. When propyltrimethoxysilane was used as the organic silane precursor mixed with tetramethoxysilane at a molar ratio of 16:1, the hybrid gel-entrapped protease on Celite 545 had 8 times the activity of the protease deposited on Celite 545 from 35 to 85°C. 相似文献
85.
Abstract The kinetics of budding/dividing of parent cells at different culture ages, spread on a fresh medium, was formulated by the following model N t = N ∞ [1 − exp (− λ ( t − t r) ] where N t is the number of budding/dividing cells in the parent population at time t , N ∞ is the expected number of budding/dividing cells at infinite time, λ is the rate of budding/dividing of parent cells, and t r is the retardation time. The rate of budding/dividing λ decreased with the increase in the culture age of the parent cell population. 相似文献
86.
Tanaka T Ishii T Mizuno D Mori T Yamaji R Nakamura Y Kumazawa S Nakayama T Akagawa M 《Free radical biology & medicine》2011,50(10):1324-1335
(-)-Epigallocatechin-3-gallate (EGCG), the most abundant and biologically active polyphenol in green tea, induces apoptosis and suppresses proliferation of cancer cells by modulating multiple signal transduction pathways. However, the fundamental mechanisms responsible for these cancer-preventive effects have not been clearly elucidated. Recently, we found that EGCG can covalently bind to cysteine residues in proteins through autoxidation and subsequently modulate protein function. In this study, we demonstrate the direct binding of EGCG to cellular proteins in AZ521 human gastric cancer cells by redox-cycle staining. We comprehensively explored the binding targets of EGCG from EGCG-treated AZ521 cells by proteomics techniques combined with the boronate-affinity pull-down method. The DEAD-box RNA helicase p68, which is overexpressed in a variety of tumor cells and plays an important role in cancer development and progression, was identified as a novel EGCG-binding target. Exposure of AZ521 cells to EGCG lowered the p68 level dose dependently. The present findings show that EGCG inhibits AZ521 cell proliferation by preventing β-catenin oncogenic signaling through proteasomal degradation of p68 and provide a new perspective on the molecular mechanism of EGCG action. 相似文献
87.
Tsutomu Akama Charlotte Virtucio Chen Dong Richard Kimura Yong-Kang Zhang James A. Nieman Rashmi Sharma Xiaosong Lu Marcelo Sales Rajeshwar Singh Anne Wu Xiao-Qing Fan Liang Liu Jacob J. Plattner Kurt Jarnagin Yvonne R. Freund 《Bioorganic & medicinal chemistry letters》2013,23(6):1680-1683
A series of novel 6-(aminomethylphenoxy)benzoxaborole analogs was synthesized for the investigation of the structure–activity relationship of the inhibition of TNF-alpha, IL-1beta, and IL-6, from lipopolysaccharide stimulated peripheral blood mononuclear cells. Compounds 9d and 9e showed potent activity against all three cytokines with IC50 values between 33 and 83 nM. Chloro substituted analog 9e (AN3485) is considered to be a promising lead for novel anti-inflammatory agent with a favorable pharmacokinetic profile. 相似文献
88.
Takeshi Ishii Tomoe Yamada Taiki Mori Shigenori Kumazawa Koji Uchida Tsutomu Nakayama 《Free radical research》2013,47(11):1253-1260
Lipid peroxidation products contribute to protein aggregation that occurs during oxidative stress in a number of degenerative disorders. Acrolein (ACR), a highly toxic lipid peroxidation aldehyde, is a strong cross-linking agent of cellular components such as proteins. To understand the mechanisms of oxidative stress-induced protein aggregation, this study characterized the ACR modification of chain B from bovine insulin by mass spectrometry. To identify the cross-linking sites, the ACR-treated peptide was digested with a protease and the resulting peptides were analysed by liquid chromatography-tandem mass spectrometry. Inter- and intra-molecular cross-linking adducts were identified between amino groups and the side chain of histidine in the peptide. These results indicated that the ACR-induced cross-links were accompanied by two reactions, namely Michael addition and Schiff base formation. In conclusion, the use of mass spectrometric techniques provided chemical evidence for protein cross-linking with ACR. 相似文献
89.
Exposure to high‐concentration oxygen in the neonatal period induces abnormal retinal vascular patterning in mice 下载免费PDF全文
Akane Morita Hiroko Ushikubo Asami Mori Kenji Sakamoto Tsutomu Nakahara 《Birth defects research. Part B, Developmental and reproductive toxicology》2016,107(6):216-224
The interruption of vascular development could cause structural and functional abnormalities in tissues. We have previously reported that short‐term treatment of newborn mice with vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors induces abnormal retinal vascular growth and patterns. An exposure of neonatal mice to high‐concentration oxygen disturbs normal retinal vascular development. The present study aimed to determine (1) whether vascular abnormalities are observed in the retina of newborn mice exposed to high concentrations of oxygen, and (2) how astrocyte network formation is affected following the exposure to hyperoxia. Newborn (postnatal day 0) mice were exposed to 75% oxygen for 48 or 96 hr. During hyperoxia exposure, VEGF expression decreased, and the onset of retinal vascularization was completely suppressed. After completion of the hyperoxic period, retinal vascularization occurred, but it was delayed in a hyperoxic exposure duration‐dependent manner. In retinas of hyperoxia‐exposed mice, dense capillary plexuses were found, and the number of arteries and veins decreased. The astrocyte network formation was slightly delayed under hyperoxic conditions, and the network became denser in retinas of mice with an episode of hyperoxia. Expression of VEGF levels in the avascular retina of mice that were exposed to hyperoxia was higher than that of control mice. These results suggest that short‐term interruption of the onset of vascular development resulting from the reduction in VEGF signals induces abnormal vascular patterns in the mouse retina. The abnormalities in retinal astrocyte behavior might contribute to the formation of an abnormal retinal vascular growth. 相似文献
90.
Chikara Komiya Kyoichiro Tsuchiya Kumiko Shiba Yasutaka Miyachi Shunsaku Furuke Noriko Shimazu Shinobu Yamaguchi Kazuo Kanno Yoshihiro Ogawa 《PloS one》2016,11(3)
Type 2 diabetes mellitus (T2DM) is associated with a high incidence of non-alcoholic fatty liver disease (NAFLD) related to obesity and insulin resistance. Currently, medical interventions for NAFLD have focused on diet control and exercise to reduce body weight, and there is a requirement for effective pharmacological therapies. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are oral antidiabetic drugs that promote the urinary excretion of glucose by blocking its reabsorption in renal proximal tubules. SGLT2 inhibitors lower blood glucose independent of insulin action and are expected to reduce body weight because of urinary calorie loss. Here we show that an SGLT2 inhibitor ipragliflozin improves hepatic steatosis in high-fat diet-induced and leptin-deficient (ob/ob) obese mice irrespective of body weight reduction. In the obese mice, ipragliflozin-induced hyperphagia occurred to increase energy intake, attenuating body weight reduction with increased epididymal fat mass. There is an inverse correlation between weights of liver and epididymal fat in ipragliflozin-treated obese mice, suggesting that ipragliflozin treatment promotes normotopic fat accumulation in the epididymal fat and prevents ectopic fat accumulation in the liver. Despite increased adiposity, ipragliflozin ameliorates obesity-associated inflammation and insulin resistance in epididymal fat. Clinically, ipragliflozin improves liver dysfunction in patients with T2DM irrespective of body weight reduction. These findings provide new insight into the effects of SGLT2 inhibitors on energy homeostasis and fat accumulation and indicate their potential therapeutic efficacy in T2DM-associated hepatic steatosis. 相似文献