全文获取类型
收费全文 | 5899篇 |
免费 | 428篇 |
国内免费 | 6篇 |
出版年
2024年 | 8篇 |
2023年 | 27篇 |
2022年 | 98篇 |
2021年 | 129篇 |
2020年 | 100篇 |
2019年 | 117篇 |
2018年 | 204篇 |
2017年 | 160篇 |
2016年 | 253篇 |
2015年 | 396篇 |
2014年 | 396篇 |
2013年 | 441篇 |
2012年 | 570篇 |
2011年 | 508篇 |
2010年 | 305篇 |
2009年 | 277篇 |
2008年 | 369篇 |
2007年 | 376篇 |
2006年 | 299篇 |
2005年 | 265篇 |
2004年 | 251篇 |
2003年 | 229篇 |
2002年 | 163篇 |
2001年 | 94篇 |
2000年 | 81篇 |
1999年 | 68篇 |
1998年 | 29篇 |
1997年 | 25篇 |
1996年 | 14篇 |
1995年 | 14篇 |
1994年 | 8篇 |
1993年 | 6篇 |
1992年 | 8篇 |
1991年 | 8篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 5篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 3篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1971年 | 2篇 |
排序方式: 共有6333条查询结果,搜索用时 15 毫秒
1.
In the present study, non‐thermal dielectric barrier discharge (DBD) plasma of induced structural changes of morin resulted in the isolation of one previously undescribed benzofuranone derivative, along with two known compounds. The chemical structures of these degradation products were elucidated by UV, NMR and FAB‐MS spectroscopic analyses. The isolated three compounds showed potent antioxidative activities in two different tests, with IC50 values in the range of 12.9–41.8 μm in the 2,2′‐azino‐bis (3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS+) radical scavenging activity, 19.0–71.9 μm for hydroxyl radical scavenging activity test. Furthermore, the new methoxylated benzofuranone exhibited enhancement of inhibitory effects against pancreatic lipase with an IC50 value of 90.7±1.6 μm , when compared to the parent morin. These results suggested that the degradation products isolated from plasma exposed morin might be beneficial for prevention of obesity and related diseases. 相似文献
2.
Blocking of acidosis-mediated apoptosis by a reduction of lactate dehydrogenase activity through antisense mRNA expression. 总被引:3,自引:0,他引:3
D Jeong T S Kim J W Lee K T Kim H J Kim I H Kim I Y Kim 《Biochemical and biophysical research communications》2001,289(5):1141-1149
Lactic acid produced from the cells is a potential cause of extra- and intracellular acidification. Due to scarce technical tools, lactic acid that leads to acidification could not be reduced and direct evidence of the relationship between metabolic lactate and apoptosis has not yet been elucidated. In this study, we designed a cellular pH regulation system in CHO cells by a reduction of lactate dehydrogenase (LDH) activity through LDH antisense mRNA expression. This inhibited lactate production and, therefore, acidification of the cytosol. Under HCO3(-)-buffered growth conditions, both the parent CHO cells and the engineered CHO cells maintained their extracellular pH and intracellular pH fairly well. However, upon acidification of the cytosol, only the parent CHO cells underwent apoptosis under HCO3(-)-free conditions. In fact, we observed a number of apoptosis-related events only in control cells, including mitochondrial dysfunction, cytochrome c release, and an increase in caspase-3 enzymatic activity. 相似文献
3.
Bo Ram Kim Ji-Young Park Hyung Jae Jeong Hyung-Jun Kwon Su-Jin Park In-Chul Lee 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):1256-1265
Sialidases are key virulence factors that remove sialic acid from the host cell surface glycan, unmasking receptors that facilitate bacterial adherence and colonisation. In this study, we developed potential agents for treating bacterial infections caused by Streptococcus pneumoniae Nan A that inhibit bacterial sialidase using Turmeric and curcumin analogues. Design, synthesis, and structure analysis relationship (SAR) studies have been also described. Evaluation of the synthesised derivatives demonstrated that compound 5e was the most potent inhibitor of S. pneumoniae sialidase (IC50?=?0.2?±?0.1?µM). This compound exhibited a 3.0-fold improvement in inhibitory activity over that of curcumin and displayed competitive inhibition. These results warrant further studies confirming the antipneumococcal activity 5e and indicated that curcumin derivatives could be potentially used to treat sepsis by bacterial infections. 相似文献
4.
Advanced hepatic fibrosis therapy using drug-delivering nanoparticles is a relatively unexplored area. Angiotensin type 1 (AT1) receptor blockers such as losartan can be delivered to hepatic stellate cells (HSC), blocking their activation and thereby reducing fibrosis progression in the liver. In our study, we analyzed the possibility of utilizing drug-loaded vehicles such as hyaluronic acid (HA) micelles carrying losartan to attenuate HSC activation. Losartan, which exhibits inherent lipophilicity, was loaded into the hydrophobic core of HA micelles with a 19.5% drug loading efficiency. An advanced liver fibrosis model was developed using C3H/HeN mice subjected to 20 weeks of prolonged TAA/ethanol weight-adapted treatment. The cytocompatibility and cell uptake profile of losartan-HA micelles were studied in murine fibroblast cells (NIH3T3), human hepatic stellate cells (hHSC) and FL83B cells (hepatocyte cell line). The ability of these nanoparticles to attenuate HSC activation was studied in activated HSC cells based on alpha smooth muscle actin (α-sma) expression. Mice treated with oral losartan or losartan-HA micelles were analyzed for serum enzyme levels (ALT/AST, CK and LDH) and collagen deposition (hydroxyproline levels) in the liver. The accumulation of HA micelles was observed in fibrotic livers, which suggests increased delivery of losartan compared to normal livers and specific uptake by HSC. Active reduction of α-sma was observed in hHSC and the liver sections of losartan-HA micelle-treated mice. The serum enzyme levels and collagen deposition of losartan-HA micelle-treated mice was reduced significantly compared to the oral losartan group. Losartan-HA micelles demonstrated significant attenuation of hepatic fibrosis via an HSC-targeting mechanism in our in vitro and in vivo studies. These nanoparticles can be considered as an alternative therapy for liver fibrosis. 相似文献
5.
Pasupathi Sundaramoorthy Jae Jun Sim Yeong-Su Jang Siddhartha Kumar Mishra Keun-Yeong Jeong Poonam Mander Oh Byung Chul Won-Sik Shim Seung Hyun Oh Ky-Youb Nam Hwan Mook Kim 《PloS one》2015,10(1)
Cancer cell motility is a key phenomenon regulating invasion and metastasis. Focal adhesion kinase (FAK) plays a major role in cellular adhesion and metastasis of various cancers. The relationship between dietary supplementation of calcium and colon cancer has been extensively investigated. However, the effect of calcium (Ca2+) supplementation on calpain-FAK-motility is not clearly understood. We sought to identify the mechanism of FAK cleavage through Ca2+ bound lactate (CaLa), its downstream signaling and role in the motility of human colon cancer cells. We found that treating HCT116 and HT-29 cells with CaLa immediately increased the intracellular Ca2+ (iCa2+) levels for a prolonged period of time. Ca2+ influx induced cleavage of FAK into an N-terminal FAK (FERM domain) in a dose-dependent manner. Phosphorylated FAK (p-FAK) was also cleaved in to its p-N-terminal FAK. CaLa increased colon cancer cells motility. Calpeptin, a calpain inhibitor, reversed the effects of CaLa on FAK and pFAK cleavage in both cancer cell lines. The cleaved FAK translocates into the nucleus and modulates p53 stability through MDM2-associated ubiquitination. CaLa-induced Ca2+ influx increased the motility of colon cancer cells was mediated by calpain activity through FAK and pFAK protein destabilization. In conclusion, these results suggest that careful consideration may be given in deciding dietary Ca2+ supplementation to patient undergoing treatment for metastatic cancer. 相似文献
6.
7.
Indirect evidence suggests that legumes can adjust rapidly theresistance of their root nodules to O2 diffusion. Here we describeexperiments using O2 specific micro-electrodes and dark fieldmicroscopy to study directly the operation of this diffusionbarrier. The O2 concentration sensed by the electrode decreasedsharply in the region of the inner cortex and was less than1.0 mmol m3 throughout the infected tissue in nodulesof both pea (Pisum sativum) and french bean (Phaseolus vulgaris).In a number of experiments the ambient O2 concentration wasincreased to 40% while the electrode tip was just inside theinner cortex. In 13 out of 21 cases the O2 concentration atthis position either remained low and unchanged or increasedirreversibly to near ambient values. In the remaining casesthe O2 concentration increased after 1 to 2.5 min and then decreasedto its former value. These results are ascribed to an increasein resistance of the barrier in response to increased O2 fluxinto the nodule. It was shown microscopically that air spacesboth at the boundary between the infected zone and the innercortex, and within the infected zone started to disappear 3min after nodules were exposed to high ambient O2 concentrationsand had disappeared completely after 8 min. These spaces werenot changed by exposure of the nodule for 10 min to either N2or air. Key words: Oxygen, root nodules, air spaces 相似文献
8.
Evolution of the 28S ribosomal RNA gene in anurans: regions of variability and their phylogenetic implications 总被引:1,自引:0,他引:1
Fifteen restriction sites were mapped to the 28S ribosomal RNA gene of
individuals representing 54 species of frogs, two species of salamanders, a
caecilian, and a lungfish. Eight of these sites were present in all species
examined, and two were found in all but one species. Alignment of these
conserved restriction sites revealed, among anuran 28S rRNA genes, five
regions of major length variation that correspond to four of 12 previously
identified divergent domains of this gene. One of the divergent domains
(DD8) consists of two regions of length variation separated by a short
segment that is conserved at least throughout tetrapods. Most of the
insertions, deletions, and restriction-site variations identified in the
28S gene will require sequence-level analysis for a detailed reconstruction
of their history. However, an insertion in DD9 that is coextensive with
frogs in the suborder Neobatrachia, a BstEII site that is limited to
representatives of two leptodactylid subfamilies, and a deletion in DD10
that is found only in three ranoid genera are probably synapomorphies.
相似文献
9.
The experiment was conducted to investigate the human thermoregulatory responses during rest, exercise and recovery atT
a 20°C and 60% R.H. under the conditions of wearing two different types of clothing. Six healthy men wore two types of clothing: one covering the whole body area except the head (Type A, weight 1656 g), and the other covering only the trunk, upper arms and thighs (Type B, weight 996 g). The level of rectal temperature was kept significantly higher in Type B than in Type A during rest and recovery. The increased and decreased rates of rectal temperature during exercise and recovery were significantly greater in Type A than in Type B, respectively. These findings are discussed from the viewpoint of the differences of skin temperatures of the extremities between Type A and Type B. 相似文献
10.
Strain-dependent expression of VH gene families 总被引:12,自引:0,他引:12
H D Jeong J L Komisar E Kraig J M Teale 《Journal of immunology (Baltimore, Md. : 1950)》1988,140(7):2436-2441
The tremendous diversity of the antibody specificity repertoire stems from the ability of each developing B cell to select one out of many possible variable, diversity, and joining gene segments by specific rearrangement of the DNA. The mechanism by which V region gene segments is selected is not known. Moreover, evidence for both random and nonrandom expression of VH genes in mature B cells has been presented previously. In this report, the technique of in situ hybridization is used to accurately measure at the single cell level VH gene family expression in LPS-induced cells from several strains. In this way, at least one-third of the B cells are stimulated and a large sampling of activated splenocytes from each strain analyzed. The use of in situ hybridization eliminates any potential biases resulting from transformation protocols. In addition, because all populations of cells are analyzed by both in situ hybridization and immunocytochemical staining with anti-IgM, the proportion of cells detected by in situ hybridization could be compared with the proportion of B cells, blasts, and plasma cells in the population. It was concluded from these comparisons that the cells being detected by in situ hybridization under the conditions described are plasmablasts and plasma cells. Therefore, an accurate measure of the functional and expressed VH gene repertoire could be made. The results clearly demonstrate strain-dependent variation in VH gene family expression, particularly VH 7183 and VH J558 with up to three-fold differences observed. Thus, either there is considerable strain variation in the number of functional VH gene family segments or the expression of VH genes is not entirely random. 相似文献