全文获取类型
收费全文 | 3544篇 |
免费 | 202篇 |
国内免费 | 1篇 |
专业分类
3747篇 |
出版年
2022年 | 20篇 |
2021年 | 44篇 |
2020年 | 23篇 |
2019年 | 24篇 |
2018年 | 38篇 |
2017年 | 38篇 |
2016年 | 61篇 |
2015年 | 134篇 |
2014年 | 150篇 |
2013年 | 231篇 |
2012年 | 208篇 |
2011年 | 209篇 |
2010年 | 139篇 |
2009年 | 151篇 |
2008年 | 200篇 |
2007年 | 198篇 |
2006年 | 240篇 |
2005年 | 216篇 |
2004年 | 237篇 |
2003年 | 194篇 |
2002年 | 186篇 |
2001年 | 59篇 |
2000年 | 54篇 |
1999年 | 67篇 |
1998年 | 41篇 |
1997年 | 39篇 |
1996年 | 24篇 |
1995年 | 28篇 |
1994年 | 24篇 |
1993年 | 24篇 |
1992年 | 30篇 |
1991年 | 35篇 |
1990年 | 27篇 |
1989年 | 24篇 |
1988年 | 29篇 |
1987年 | 16篇 |
1986年 | 17篇 |
1985年 | 25篇 |
1984年 | 16篇 |
1983年 | 15篇 |
1982年 | 17篇 |
1981年 | 19篇 |
1979年 | 19篇 |
1978年 | 15篇 |
1976年 | 12篇 |
1973年 | 13篇 |
1971年 | 13篇 |
1969年 | 13篇 |
1968年 | 14篇 |
1966年 | 12篇 |
排序方式: 共有3747条查询结果,搜索用时 15 毫秒
91.
Summary The enzymatic characteristics and the mode of hormone-dependent stimulation of cAMP phosphodiesterase are reviewed. The hormone-sensitive phosphodiesterase is a low Km enzyme, which has been found in liver and fat cells. The fat cell enzyme is mostly associated with the endoplasmic reticulum. The liver cell enzyme is also associated with certain subcellular structures.The hormone-sensitive phosphodiesterase appears to have catalytic and regulatory domains and is thought to be attached to subcellular structures at the regulatory portion of the enzyme. The catalytic domain of the fat cell enzyme can be obtained in a soluble form from the microsomal preparation by mild proteolysis or by dithiothreitol treatment at 0–4 °C. The catalytic domain of the liver enzyme can be solubilized by either hypotonic treatment or mild trypsin digestion. The catalytic domains solubilized from the basal and hormonally activated forms of the enzyme are apparently identical.The membrane-bound basal enzyme from adipocytes is activated in a concentrated salt solution without being solubilized. On the other hand, the plus-insulin activity is deactivated in a low salt solution or by a short dithiothreitol treatment at 37°, apparently without suffering any changes in the catalytic domain. In contrast, p-chloromercuriphenyl sulfonate seems to inactivate the enzyme by interacting with SH-groups in the catalytic domain. Although the liver enzyme is not similarly affected by salt concentrations, its catalytic activity is blocked by p-chloromercuribenzoate.The adipocyte enzyme can be solubilized with a mixture of Lubrol WX and Zwittergent 3–14. The apparent Stokes radius of the basal enzyme is approximately 87 A, while that of the hormone-stimulated enzyme is approximately 94 A.Apparently, the same species of phosphodiesterase is activated by both insulin and epinephrine in fat cells and by insulin and glucagon in liver, possibly being mediated by reactions involving phosphorylation. However, it is yet to be ascertained how phosphorylation is involved and how the apparent Stokes radius of the adipocyte enzyme is increased as a result of stimulation. 相似文献
92.
Regulation of angiogenesis by the aging suppressor gene klotho 总被引:5,自引:0,他引:5
Fukino K Suzuki T Saito Y Shindo T Amaki T Kurabayashi M Nagai R 《Biochemical and biophysical research communications》2002,293(1):332-337
Advanced age is a major risk factor of peripheral artery disease. We examined the effects of the aging-suppressor gene klotho on angiogenesis in response to ischemia by introducing ischemic hindlimb model in mice heterozygously deficient for the klotho gene and in wild type mice. Blood flow recovery as assessed by laser doppler perfusion imaging and angiogenesis as assessed by density of PECAM-1/CD31-positive positive capillaries were markedly impaired in mice heterozygously deficient for the klotho gene (both <0.05). Our findings show that the aging-suppressor gene klotho affects angiogenesis and the possibility that age-related impairment of angiogenesis might be regulated by the klotho gene. Our results present a new possibility of therapeutic angiogenesis for patients of advanced age. 相似文献
93.
Dear Editor:
Geldanamycin is a benzoquinone ansamycin, which was originally described as a tyrosine kinase inhibitor. However, subsequent studies have revealed that geldanamycin binds to and inhibits heat-shock protein 90 (Hsp90) activity [1]. Hsp90 is a molecular chaperone involved in the conformational maturation of proteins such as mutated p53, Raf- 1, Akt, Bcr-Abl, and ErbB2. It is suggested that agents inhibiting Hsp90 have anti-cancer properties, although the precise molecular mechanisms underlying the anti-cancer effects of geldanamycin are not well understood. 相似文献
94.
Shigeru Kitanishi Toshiaki Yamamoto Hiromi Ishii Yuko Yamaguchi Toru Kobayashi 《Ichthyological Research》2017,64(1):111-115
To evaluate the influences of spatial scale on dispersal, the dispersal patterns of masu salmon Oncorhynchus masou masou were investigated at among-river (ca. <43 km) and within-river levels in mid-western Hokkaido, Japan. A genetic differentiation (F ST) and assignment test showed that among-river dispersal was much less common (2.9 % of 339 individuals) than within-river dispersal (7.4 % of 190 individuals). We also found that there was no bias in dispersal at the among-river level, while anadromous males were more likely to disperse at the within-river level, suggesting that the dispersal patterns may be scale dependent. 相似文献
95.
Harauma A Murayama T Ikeyama K Sano H Arai H Takano R Kita T Hara S Kamei K Yokode M 《Biochemical and biophysical research communications》2007,358(3):751-756
Mulberry is commonly used to feed silkworms. Here we examined whether a dietary intake of mulberry leaf (ML) could affect atherogenesis in vivo and in vitro. Apolipoprotein E-deficient mice were fed either normal chow (control group) or a diet containing 1% ML powder (ML group) from 6 weeks of age. The mice were sacrificed after 12 weeks. The susceptibility of plasma lipoprotein to oxidation was assessed using diene formation. A significant increase in the lag time of lipoprotein oxidation was detected in the ML group compared with the control group. Furthermore, the ML group showed a 40% reduction in atherosclerotic lesion size in the aortae compared with the control. We also examined the direct anti-oxidative activity of ML in vitro. Aqueous extract of ML had a strong scavenging effect on 1,1-diphenyl-2-picrylhydrazyl and inhibited lipoprotein oxidation. These results confirm that ML contains anti-oxidative substances that might help prevent atherosclerosis. 相似文献
96.
We investigated the effect of preconditioning on ischemia-reperfusion injury in the rat bladder. Rat abdominal aorta was clamped with a small clip to induce ischemia-reperfusion injury in the bladder. Twelve-week-old male SD rats were divided into three groups; sham-operated control (Cont), 30 min ischemia-60 min reperfusion (IR) and three times of 5 min ischemia and then 30 min ischemia-60 min reperfusion (PC) groups. The bladder functions were estimated by cystometric and functional studies. Contractile response curves to increasing concentrations of carbachol were constructed in the absence and presence of various concentrations of subtype selective muscarinic antagonists, i.e. atropine (non-selective), pirenzepine (M1 selective), methoctramine (M2 selective), and 4-DAMP (M1/M3 selective). We also measured tissue levels of malonaldehyde (MDA) and examined possible histological changes in these rats' bladders. Preconditioning partially prevented the reduction of bladder dysfunction induced by ischemia-reperfusion. Estimation of the pA2 values for atropine, pirenzepine, methoctramine, and 4-DAMP indicates that the carbachol-induced contractile response in bladder dome is mediated through the M3 receptor subtype in all groups. The MDA concentration in the IR group was significantly larger than that of the control group, and preconditioning significantly reduced MDA production in the bladder. In histological studies, the ischemia-reperfusion with or without preconditioning caused infiltration of leukocytes and rupture of microcirculation in the regions of submucosa and smooth muscle without a corresponding sloughing of mucosal cells. Our data indicate that preconditioning has a beneficial effect on ischemia-reperfusion injury in the rat bladder. 相似文献
97.
98.
Chihiro Minatsuki Nobutake Yamamichi Takeshi Shimamoto Hikaru Kakimoto Yu Takahashi Mitsuhiro Fujishiro Yoshiki Sakaguchi Chiemi Nakayama Maki Konno-Shimizu Rie Matsuda Satoshi Mochizuki Itsuko Asada-Hirayama Yosuke Tsuji Shinya Kodashima Satoshi Ono Keiko Niimi Toru Mitsushima Kazuhiko Koike 《PloS one》2013,8(7)
Background
Despite the high prevalence of gastroesophageal reflux disease (GERD), its risk factors are still a subject of controversy. This is probably due to inadequate distinction between reflux esophagitis (RE) and non-erosive reflux disease (NERD), and is also due to inadequate evaluation of adjacent stomach. Our aim is therefore to define background factors of RE and NERD independently, based on the evaluation of Helicobacter pylori infection and gastric atrophy.Methods
We analyzed 10,837 healthy Japanese subjects (6,332 men and 4,505 women, aged 20–87 years) who underwent upper gastrointestinal endoscopy. RE was diagnosed as the presence of mucosal break, and NERD was diagnosed as the presence of heartburn and/or acid regurgitation in RE-free subjects. Using GERD-free subjects as control, background factors for RE and NERD were separately analyzed using logistic regression to evaluate standardized coefficients (SC), odds ratio (OR), and p-value.Results
Of the 10,837 study subjects, we diagnosed 733 (6.8%) as RE and 1,722 (15.9%) as NERD. For RE, male gender (SC = 0.557, OR = 1.75), HP non-infection (SC = 0.552, OR = 1.74), higher pepsinogen I/II ratio (SC = 0.496, OR = 1.64), higher BMI (SC = 0.464, OR = 1.60), alcohol drinking (SC = 0.161, OR = 1.17), older age (SC = 0.148, OR = 1.16), and smoking (SC = 0.129, OR = 1.14) are positively correlated factors. For NERD, HP infection (SC = 0.106, OR = 1.11), female gender (SC = 0.099, OR = 1.10), younger age (SC = 0.099, OR = 1.10), higher pepsinogen I/II ratio (SC = 0.099, OR = 1.10), smoking (SC = 0.080, OR = 1.08), higher BMI (SC = 0.078, OR = 1.08), and alcohol drinking (SC = 0.076, OR = 1.08) are positively correlated factors. Prevalence of RE in subjects with chronic HP infection and successful HP eradication denotes significant difference (2.3% and 8.8%; p<0.0001), whereas that of NERD shows no difference (18.2% and 20.8%; p = 0.064).Conclusions
Significantly associated factors of NERD are considerably different from those of RE, indicating that these two disorders are pathophysiologically distinct. Eradication of Helicobacter pylori may have disadvantageous effects on RE but not on NERD. 相似文献99.
Y Ikehara N Kojima N Kurosawa T Kudo M Kono S Nishihara S Issiki K Morozumi S Itzkowitz T Tsuda S I Nishimura S Tsuji H Narimatsu 《Glycobiology》1999,9(11):1213-1224
100.
Toru Ishikawa Satoshi Abe Asami Hoshii Yumi Yamada Akihiko Iiduka Takeo Nemoto Keiko Takeda Toshiaki Yoshida 《PloS one》2016,11(1)