全文获取类型
收费全文 | 19132篇 |
免费 | 1711篇 |
国内免费 | 1541篇 |
专业分类
22384篇 |
出版年
2024年 | 34篇 |
2023年 | 251篇 |
2022年 | 557篇 |
2021年 | 924篇 |
2020年 | 622篇 |
2019年 | 705篇 |
2018年 | 740篇 |
2017年 | 554篇 |
2016年 | 713篇 |
2015年 | 1176篇 |
2014年 | 1290篇 |
2013年 | 1393篇 |
2012年 | 1592篇 |
2011年 | 1518篇 |
2010年 | 999篇 |
2009年 | 845篇 |
2008年 | 927篇 |
2007年 | 888篇 |
2006年 | 783篇 |
2005年 | 665篇 |
2004年 | 636篇 |
2003年 | 557篇 |
2002年 | 527篇 |
2001年 | 393篇 |
2000年 | 392篇 |
1999年 | 359篇 |
1998年 | 174篇 |
1997年 | 163篇 |
1996年 | 160篇 |
1995年 | 121篇 |
1994年 | 147篇 |
1993年 | 92篇 |
1992年 | 155篇 |
1991年 | 148篇 |
1990年 | 122篇 |
1989年 | 98篇 |
1988年 | 82篇 |
1987年 | 96篇 |
1986年 | 83篇 |
1985年 | 92篇 |
1984年 | 48篇 |
1983年 | 48篇 |
1982年 | 48篇 |
1981年 | 36篇 |
1980年 | 37篇 |
1979年 | 52篇 |
1978年 | 41篇 |
1977年 | 45篇 |
1975年 | 35篇 |
1974年 | 44篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
961.
Wei CC Tian B Perry G Meng QC Chen YF Oparil S Dell'Italia LJ 《American journal of physiology. Heart and circulatory physiology》2002,282(6):H2254-H2258
We utilized mice with homozygous disruption of angiotensin-converting enzyme (ACE) (-/-), mice with heterozygous deletion of ACE (+/-), and wild-type mice (+/+) to test the hypothesis that genetic variation in ACE modulates tissue and plasma angiotensin (ANG) II concentrations. With the use of ANG I as substrate, kidney, heart, and lung ACE activity was reduced 80% in -/- mice compared with +/+ mice. However, ANG II concentrations and ANG II-to-ANG I ratios in the kidney, heart, and lung did not differ among genotypes. In contrast, plasma ANG II concentrations in -/- mice were <2 fmol/ml, whereas plasma ANG I concentrations were extremely high (765 fmol/ml). Chymase activity was increased 14-fold in the kidney (P < 0.05) and 1.5-fold in the heart (P < 0.05) of -/- versus +/+ mice but did not differ among genotypes in the lung. ANG II formation from enzymes other than ACE and chymase contributed <2% of total ANG II formation in all genotypes. These data suggest that ACE is essential to ANG II formation in the vascular space, whereas chymase may provide an important mechanism in maintaining steady-state ANG II levels in tissue. 相似文献
962.
四周模拟失重大鼠后身动脉平滑肌细胞钾电流的改变 总被引:4,自引:2,他引:2
本文采用全细胞膜片钳方法观察4周尾部悬吊大鼠(tail-suspended rats,SUS)隐动脉及肠系膜的动脉第2-6级动脉分支血管平滑肌细胞(vascular smooth muscle cells,VSMCs)钾电流密度的变化,结果表明:SUS大鼠后身动脉VSMCs的静息电位(RP)较对照大鼠(CON)后身动脉VSMCs的RP更负,SUS组隐动脉和肠系膜小鼠后身动脉VSMCs的静息电位(RP)较对照大鼠(CON)后身动脉VSMCs的RP更负,SUS组隐动脉和肠系膜小动脉VSMCs的全细胞钾电流密度较CON组显著增加,其中,SUS组的隐动脉和肠系膜小动脉VSMCs的大电导钙激活钙离子通道(BKca)和电压激活钾离子通道(Kv)电流密度较CON组的BKca和Kv电流密度均显著增加,以上结果提示,VSMCs的超极化及进一步引起的通过电压依赖性钙离子通道的钙内流减少可能是模拟失重引起后身动脉反应性降低的电生理机制之一。 相似文献
963.
Neurotoxicity is the dose-limiting side-effect of vincristine in cancer therapy. Using the nerve growth factor (NGF)-dependent
neurite outgrowth and cell proliferation of the PC12 pheochromocytoma cell line as an in vitroassay, the protective effect of different intravenous anesthetics was assessed. Vincristine (1 nmol/L) significantly decreased
the percentage of neurite-forming cells from 68%±9% to 27%±7% within a 3-day incubation period. The longer neurites (>2× cell
body) in particular proved to be extremely sensitive to vincristine (from 17%±4% to 0% of total neurite-expressing cells).
Flow cytometry results revealed an S-phase percentage of 15.85%±3.25% after NGF induction, with vincristine reducing this
percentage to 0.68%±0.38%. Reversal of the inhibitory effect of vincristine was noted in the cells treated with thiopental
or propofol but not etomidate. Bicuculline partially antagonized the protective effect of thiopental and propofol in both
studies. We conclude that thiopental and propofol, but not etomidate, have a protective effect in vincristine-induced neurotoxicity.
The protective effect produced by thiopental and propofol is probably secondary to activation of GABAAreceptors.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
964.
A water-insoluble alpha-(1-->3)-D-glucan (A) from Lentinus edodes was fractionated into 13 fractions in dimethyl sulfoxide containing 0.25 M lithium chloride (0.25 M LiCl-Me(2)SO). Five fractions were treated with sulfur trioxide-pyridine complex at 25 degrees C to synthesize water-soluble sulfated derivatives (S-A). The weight-average molecular weights, M(w), and intrinsic viscosities [eta], of the samples A and S-A were determined by multi-angler laser light scattering (MALLS), and viscosity. The M(w) dependence of [eta] and of the radius of gyration (z)(1/2), was found to be represented approximately by [eta]=4.9 x 10(-2) M(w)(0.67) (cm(3) g(-1)), and (z)(1/2)=4.8 x 10(-2) M(w)(0.54) (nm) for the alpha-glucan in 0.25 M LiCl-Me(2)SO in the M(w) range from 7.24 x 10(4) to 4.21 x 10(5), and by [eta]=6.8 x 10(-4) M(w) 1.06 (cm(3) g(-1)), and (z)(1/2)=9.4 x 10(-4) M(w)(0.92) (nm) for the sulfated alpha-glucan in aqueous 0.5 M NaCl in the M(w) range from 5.92 x 10(4) to 1.42 x 10(5) at 25 degrees C. The results indicate that the alpha-(1-->3)-D-glucan exists as a flexible chain in 0.25 M LiCl-Me(2)SO, and its sulfated derivative in 0.5 M NaCl aqueous has stiffer chains than the original. (13)C NMR indicated that intramolecular hydrogen bonding occurred in the sulfated alpha-glucan, causing the observed chain stiffness. 相似文献
965.
Morphological transformations of bolaamphiphilic polydiacetylene (L-Glu-Bis-3) lipid assemblies from helical ribbons to vesicles and flat sheets through controlled doping are described, and the role of specific lipid dopants in these processes is discussed. Upon doping with cell surface receptor G(M1) ganglioside, fluid vesicular structures start to emerge, coexisting with the micro-crystalline helical ribbons. The vesicle formation is further facilitated and stabilized by the introduction of cholesterol into the system, presumably through surface curvature variation induced by inhomogeneous distribution and dynamic clustering of G(M1) and cholesterol within the doped assemblies. Extended helical ribbons are "truncated" into patches of flat sheets when a sufficient amount of Bis-1, a structurally compatible symmetric bolaamphiphilic diacetylene lipid, is doped. The results reaffirm the important roles of packing geometry and headgroup chirality in the formation of extended helical ribbon structures. The doped assemblies of bolaamphiphiles allow for capture of intermediate structures of morphological transformation using transmission electron microscopy (TEM). A vesicle-to-ribbon transformation mechanism via lateral reorganization within relatively fluid vesicular microstructures has been suggested. Understanding of the doping-induced transformation process provides useful information for the design of advanced materials where the microscopic morphology of material is crucial to its function. 相似文献
966.
967.
968.
Regulation of MTP expression in developing swine 总被引:2,自引:0,他引:2
Lu S Huffman M Yao Y Mansbach CM Cheng X Meng S Black DD 《Journal of lipid research》2002,43(8):1303-1311
To define the developmental expression of microsomal triglyceride transfer protein (MTP) large subunit mRNA and protein, samples of small intestine and liver were collected from 40-day gestation fetal, 2-day-old newborn, 3-week-old suckling, and 2-month-old weanling swine. In fetal animals, MTP mRNA expression was high in intestine and liver. Postnatally, jejunal expression paralleled the intake of a high-fat breast milk diet and declined after weaning. Ileal expression was comparable with that of jejunum in 2-day-old animals, but declined to low levels afterward. Hepatic expression declined postnatally and remained low. MTP protein expression generally paralleled mRNA expression, except in fetal intestine in which no 97 kDa protein was detected. In 2-day-old piglets, a high-triacylglycerol diet increased jejunal and ileal MTP mRNA levels, as compared to a low-triacylglycerol diet. To test the roles of glucocorticoids and fatty acids in MTP regulation, a newborn swine enterocyte cell line (IPEC-1) was used. Except at day 2 of differentiation, dexamethasone did not influence MTP expression. Fatty acids either up-regulated or down-regulated MTP expression, depending on the specific fatty acid and duration of exposure. Although programmed genetic cues regulate MTP expression during development, clearly the amount and fatty acid composition of dietary lipid also play regulatory roles. 相似文献
969.
Qi JC Stevens RL Wadley R Collins A Cooley M Naif HM Nasr N Cunningham A Katsoulotos G Wanigasek Y Roufogalis B Krilis SA 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(8):4127-4134
AIDS patients often contain HIV-1-infected mast cells (MCs)/basophils in their peripheral blood, and in vivo-differentiated MCs/basophils have been isolated from the blood of asthma patients that are HIV-1 susceptible ex vivo due to their surface expression of CD4 and varied chemokine receptors. Because IL-16 is a ligand for CD4 and/or an undefined CD4-associated protein, the ability of this multifunctional cytokine to regulate the development of human MCs/basophils from nongranulated progenitors residing in cord or peripheral blood was evaluated. After 3 wk of culture in the presence of c-kit ligand, IL-16 induced the progenitors residing in the blood of normal individuals to increase their expression of chymase and tryptase about 20-fold. As assessed immunohistochemically, >80% of these tryptase(+) and/or chymase(+) cells expressed CD4. The resulting cells responded to IL-16 in an in vitro chemotaxis assay, and this biologic response could be blocked by anti-IL-16 and anti-CD4 Abs as well as by a competitive peptide inhibitor corresponding to a sequence in the C-terminal domain of IL-16. The additional finding that IL-16 induces calcium mobilization in the HMC-1 cell line indicates that IL-16 acts directly on MCs and their committed progenitors. IL-16-treated MCs/basophils also are less susceptible to infection by an M/R5-tropic strain of HIV-1. Thus, IL-16 regulates MCs/basophils at a number of levels, including their vulnerability to retroviral infection. 相似文献
970.
Lee HM Wang C Hu Z Greeley GH Makalowski W Hellmich HL Englander EW 《Journal of neurochemistry》2002,80(5):928-937
Hypoxia-associated, acutely reduced blood oxygenation can compromise energy metabolism, alter oxidant/antioxidant balance and damage cellular components, including DNA. We show in vivo, in the rat brain that respiratory hypoxia leads to formation of the oxidative DNA lesion, 8-hydroxy-2'-deoxyguanosine (oh8dG), a biomarker for oxidative DNA damage and to increased expression of a DNA repair enzyme involved in protection of the genome from the mutagenic consequences of oh8dG. The enzyme is a homolog of the Escherichia coli MutY DNA glycosylase (MYH), which excises adenine residues misincorporated opposite the oxidized base, oh8dG. We have cloned a full-length rat MYH (rMYH) cDNA, which encodes 516 amino acids, and by in situ hybridization analysis obtained expression patterns of rMYH mRNA in hippocampal, cortical and cerebellar regions. Ensuing hypoxia, mitochondrial DNA damage was induced and rMYH expression strongly elevated. This is the first evidence for a regulated expression of a DNA repair enzyme in the context of respiratory hypoxia. Our findings support the premise that oxidative DNA damage is repaired in neurons and the possibility that the hypoxia-induced expression of a DNA repair enzyme in the brain represents an adaptive mechanism for protection of neuronal DNA from injurious consequences of disrupted energy metabolism and oxidant/antioxidant homeostasis. 相似文献