全文获取类型
收费全文 | 3613篇 |
免费 | 225篇 |
国内免费 | 1篇 |
出版年
2021年 | 29篇 |
2019年 | 20篇 |
2018年 | 37篇 |
2017年 | 34篇 |
2016年 | 61篇 |
2015年 | 71篇 |
2014年 | 95篇 |
2013年 | 336篇 |
2012年 | 177篇 |
2011年 | 163篇 |
2010年 | 110篇 |
2009年 | 129篇 |
2008年 | 175篇 |
2007年 | 206篇 |
2006年 | 174篇 |
2005年 | 171篇 |
2004年 | 181篇 |
2003年 | 179篇 |
2002年 | 191篇 |
2001年 | 82篇 |
2000年 | 72篇 |
1999年 | 63篇 |
1998年 | 56篇 |
1997年 | 48篇 |
1996年 | 34篇 |
1995年 | 36篇 |
1994年 | 39篇 |
1993年 | 47篇 |
1992年 | 55篇 |
1991年 | 48篇 |
1990年 | 40篇 |
1989年 | 33篇 |
1988年 | 43篇 |
1987年 | 39篇 |
1986年 | 28篇 |
1985年 | 31篇 |
1984年 | 35篇 |
1983年 | 35篇 |
1982年 | 33篇 |
1981年 | 40篇 |
1980年 | 33篇 |
1979年 | 34篇 |
1978年 | 35篇 |
1977年 | 23篇 |
1976年 | 26篇 |
1975年 | 19篇 |
1974年 | 27篇 |
1973年 | 20篇 |
1972年 | 15篇 |
1967年 | 14篇 |
排序方式: 共有3839条查询结果,搜索用时 265 毫秒
251.
Esaki H Noda K Otsuki N Kojima A Asai T Tamura Y Takahashi T 《Journal of microbiological methods》2004,58(1):131-134
A total of 63 isolates were screened for the gyrA mutation (87Asp-Tyr) in Salmonella enterica serovars using real time PCR. All of the isolates were successfully identified as resistant or susceptible, consistent with the MIC result of the agar dilution method and gyrA sequencing. 相似文献
252.
An RNA-dependent protein kinase is involved in tunicamycin-induced apoptosis and Alzheimer's disease
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Onuki R Bando Y Suyama E Katayama T Kawasaki H Baba T Tohyama M Taira K 《The EMBO journal》2004,23(4):959-968
Various types of stress, such as disruption of calcium homeostasis, inhibition of protein glycosylation and reduction of disulfide bonds, result in accumulation of misfolded proteins in the endoplasmic reticulum (ER). The initial cellular response involves removal of such proteins by the ER, but excessive and/or long-term stress results in apoptosis. In this study, we used a randomized ribozyme library and ER stress-mediated apoptosis (tunicamycin-induced apoptosis) in SK-N-SH human neuroblastoma cells as a selective phenotype to identify factors involved in this process. We identified a double-stranded RNA-dependent protein kinase (PKR) as one of the participants in this process. The level of nuclear PKR was elevated, but the level of cytoplasmic PKR barely changed in tunicamycin-treated SK-N-SH cells. Furthermore, tunicamycin also raised levels of phosphorylated PKR in the nucleus. We also detected the accumulation of phosphorylated PKR in the nuclei of autopsied brain tissues in Alzheimer's disease. Thus, PKR might play a role in ER stress-induced apoptosis and in Alzheimer's disease. 相似文献
253.
Two new synthetic analogues of luotonins A and F, 7-acetylaminoluotonin A (6) and 3-[3H(quinazolino-4-one)]quinoline (7) were synthesized. The new analogues, along with four natural quinazoline-quinoline alkaloids, luotonins A (1), B (2), E (3), F (4) and a synthetic deoxoluotonin F (5), showed cytotoxic activity (IC(50) 1.8-40.0 microg/mL) and DNA topoisomerase II inhibition at a concentration of 25 microM. 相似文献
254.
Hsu PI Li CN Tseng HH Lai KH Hsu PN Lo GH Lo CC Yeh JJ Ger LP Hsiao M Yamaoka Y Hwang IR Chen A 《Helicobacter》2004,9(6):605-613
BACKGROUND: The host genetic factors that determine the clinical outcomes for Helicobacter pylori-infected individuals remain unclear. AIMS: To elucidate the relations among interleukin-1 locus polymorphisms, and H. pylori infection in the development of duodenal ulcers. MATERIALS AND METHODS: In a case-control study involving 168 control subjects and 147 patients with duodenal ulcer, biallelic polymorphisms of two interleukin-1 loci, IL-1B(-511) and IL-1B(+3954), as well as the penta-allelic variable number of tandem repeats of interleukin-1 receptor antagonist IL-1RN, were genotyped, and the H. pylori states of controls and patients were examined. RESULTS: Helicobacter pylori infection, male gender and the carriage of IL-1RN*2 independently increased the risk of duodenal ulcer with odds ratios of 6.4 (95% confidence interval, 3.7-11.0), 1.9 (95% confidence interval, 1.1-3.4) and 2.7 (95% confidence interval, 1.1-6.8), respectively. Statistical analysis revealed an interaction between IL-1RN*2 and H. pylori infection with the duodenal ulcer risk conferred by the H. pylori infection substantially increased (odds ratios, 22.6; 95% confidence interval, 5.9-86.5) by the carriage of IL-1RN*2. In addition, a synergistic interaction between IL-1RN*2 and blood group O existed. The combined risk of H. pylori infection, the carriage of IL-1RN*2 and blood group O for duodenal ulcer was 27.5 (95% confidence interval, 3.1-243.6). CONCLUSIONS: This work is the first to verify IL-1RN*2 as an independent factor that governs the development of duodenal ulcers. Our data indicate that H. pylori infection and IL-1RN*2 synergistically determine susceptibility to duodenal ulcer. The blood group phenotype is possibly a crucial determinant for the outcome of the impact of an interleukin-1 locus polymorphism on H. pylori-infected individuals. 相似文献
255.
Kitabayashi T Demura S Noda M Yamada T 《Journal of PHYSIOLOGICAL ANTHROPOLOGY and Applied Human Science》2004,23(4):111-118
This study aimed to examine gender differences in 4 body-sway factors of the center of foot pressure (CFP) during a static upright posture and the influence of alcohol intake on them. Four body-sway factors were interpreted in previous studies using factor analysis (the principal factor method and oblique solution by promax-rotation) on 220 healthy young males and females as follows; unit time sway, front-back sway, left-right sway and high frequency band power. The CFP measurement for 1 min was carried out twice with 1 min rest. The measurements of blood pressure, heart rate, whole body reaction time, standing on one leg with eyes closed, and CFP were carried out before and after the alcohol intake using 11 healthy young males and females. The measurement device used was an Anima's stabilometer G5500. The data sampling frequency was 20 Hz. Reliability of 4 body-sway factors was very high. Significant gender differences were found in the left-right sway and the high frequency band power factors, but the influence on body-sway is, as a whole, can be disregarded. These four sway factors can determine the influence of alcohol intake as efficient as 32 sway parameters. 相似文献
256.
Xue Y Hieda Y Kimura K Takayama K Fujihara J Tsujino Y 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2004,811(1):53-58
Kinetic characteristics and toxic effects of benzalkonium chloride (BZK) following injection via jugular vein (JV), femoral artery (FA) and oral administration (PO) were experimentally investigated using rats. The BZK concentrations in blood and tissues (lung, liver and kidney) were determined by high-performance liquid chromatography with solid phase extraction. Toxic doses of 15 and 250 mg/kg of BZK were used for intravascular (JV and FA) and PO administration, respectively. The fatal effects appeared soon after the dose in JV-rats, while delayed in FA- or PO-rats. The blood BZK concentrations and the elimination half-lives were similar between JV- and FA-rats, while the distribution of BZK in tissues was slightly different. In PO administration, the rats that aspirated BZK into their lungs had some symptoms, while the rats that did not aspirate BZK appeared to be normal. The BZK concentrations in blood and tissues were significantly higher in the aspirated PO-rats. The toxic degree of BZK was correlated with the BZK concentration in orally dosed rats. Lung and kidney had higher BZK concentrations compared to blood or liver, and they could be the target organs of BZK.Keyword: Benzalkonium chloride 相似文献
257.
BIG2, a guanine nucleotide exchange factor for ADP-ribosylation factors: its localization to recycling endosomes and implication in the endosome integrity 总被引:1,自引:0,他引:1
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)
Small GTPases of the ADP-ribosylation factor (ARF) family play a key role in membrane trafficking by regulating coated vesicle formation, and guanine nucleotide exchange is essential for the ARF function. Brefeldin A blocks the ARF-triggered coat assembly by inhibiting the guanine nucleotide exchange on ARFs and causes disintegration of the Golgi complex and tubulation of endosomal membranes. BIG2 is one of brefeldin A-inhibited guanine nucleotide exchange factors for the ARF GTPases and is associated mainly with the trans-Golgi network. In the present study, we have revealed that another population of BIG2 is associated with the recycling endosome and found that expression of a catalytically inactive BIG2 mutant, E738K, selectively induces membrane tubules from this compartment. We also have shown that BIG2 has an exchange activity toward class I ARFs (ARF1 and ARF3) in vivo and inactivation of either ARF exaggerates the BIG2(E738K)-induced tubulation of endosomal membranes. These observations together indicate that BIG2 is implicated in the structural integrity of the recycling endosome through activating class I ARFs. 相似文献
258.
Evidence that exogenous substances can be phagocytized by alveolar epithelial cells and transported into blood capillaries 总被引:3,自引:0,他引:3
Kato T Yashiro T Murata Y Herbert DC Oshikawa K Bando M Ohno S Sugiyama Y 《Cell and tissue research》2003,311(1):47-51
Since the ability of alveolar epithelial cells to ingest inhaled fine particles has not been characterized in detail, the present study seeks to evaluate this physiological activity. We used a 0.2% suspension of intact or lecithin-coated polystyrene latex beads (240 nm in diameter). A 5-ml suspension of intact or lecithin-coated latex beads was intratracheally administered to rats using a compressor nebulizer. Thereafter, the lungs were perfused intratracheally with glutaraldehyde solution and cut into small pieces. The samples were postfixed with osmium tetroxide, embedded in epoxy resin and examined under an electron microscope. Both lecithin-coated and uncoated beads were incorporated into alveolar macrophages. Some of the ingested beads in the alveolar macrophages were sequestered within lysosomes. Types I and II alveolar epithelial cells selectively incorporated only lecithin-coated beads, which were also observed within the cytoplasm of monocytes in the capillary lumen. These findings suggest that alveolar epithelial cells can incorporate exogenous particles, which are then transferred from the alveoli to intravascular spaces by transcytosis. 相似文献
259.
Ando Y Liang Y Ishigaki S Niwa J Jiang Y Kobayashi Y Yamamoto M Doyu M Sobue G 《Neurochemical research》2003,28(6):839-846
Amyotrophic lateral sclerosis is characterized by selective motor neuron degeneration. An apoptotic pathway is thought to be involved. It is difficult, however, to analyze the molecular pathogenic mechanism in single motor neurons because of complexity in the neural tissue, which consists of multiple lineages of cells neighboring motor neurons. We quantified the caspase-1 and -3 mRNA in single motor neurons and neighboring glial cells isolated from the spinal ventral horn of mutant SOD1 transgenic (Tg) mice and littermates. Motor neurons and neighboring glial cells were isolated from spinal sections by laser microdissection, and the mRNAs were quantified by RT-PCR. In the Tg mice, caspase-1 mRNA was first upregulated in motor neurons and second in glial cells. The caspase-3 mRNA was increased in motor neurons following the caspase-1 mRNA. These results indicated that caspase-1 and -3 mRNAs are differentially upregulated in motor neurons and glial cells of the Tg mice, and that mRNAs in isolated cells can be accurately assessed using our procedures. 相似文献
260.
Structural studies of [2',6'-dimethyl-L-tyrosine1]endomorphin-2 analogues: enhanced activity and cis orientation of the Dmt-Pro amide bond 总被引:1,自引:0,他引:1
Okada Y Fujita Y Motoyama T Tsuda Y Yokoi T Li T Sasaki Y Ambo A Jinsmaa Y Bryant SD Lazarus LH 《Bioorganic & medicinal chemistry》2003,11(9):1983-1994
Analogues of endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH(2)) (1) were designed to examine the importance of each residue on mu-opioid receptor interaction. Replacement of Tyr(1) by 2',6'-dimethyl-L-tyrosine (Dmt) (9-12) exerted profound effects: [Dmt(1)]EM-2 (9) elevated mu-opioid affinity 4.6-fold (K(i mu=0.15 nM) yet selectivity fell 330-fold as delta-affinity rose (K(i)delta=28.2 nM). This simultaneous increased mu- and delta-receptor bioactivities resulted in dual agonism (IC(50)=0.07 and 1.87 nM, respectively). While substitution of Phe(4) by a phenethyl group (4) decreased mu affinity (K(i)mu=13.3 nM), the same derivative containing Dmt (12) was comparable to EM-2 but also acquired weak delta antagonism (pA(2)=7.05). 1H NMR spectroscopy revealed a trans configuration (1:2 to 1:3, cis/trans) in the Tyr-Pro amide bond, but a cis configuration (5:3 to 13:7, cis/trans) with Dmt-Pro analogues. 相似文献