全文获取类型
收费全文 | 10497篇 |
免费 | 776篇 |
国内免费 | 11篇 |
专业分类
11284篇 |
出版年
2023年 | 44篇 |
2022年 | 135篇 |
2021年 | 205篇 |
2020年 | 153篇 |
2019年 | 188篇 |
2018年 | 260篇 |
2017年 | 215篇 |
2016年 | 384篇 |
2015年 | 604篇 |
2014年 | 628篇 |
2013年 | 706篇 |
2012年 | 921篇 |
2011年 | 842篇 |
2010年 | 566篇 |
2009年 | 492篇 |
2008年 | 687篇 |
2007年 | 615篇 |
2006年 | 557篇 |
2005年 | 477篇 |
2004年 | 498篇 |
2003年 | 408篇 |
2002年 | 329篇 |
2001年 | 171篇 |
2000年 | 150篇 |
1999年 | 137篇 |
1998年 | 72篇 |
1997年 | 65篇 |
1996年 | 49篇 |
1995年 | 38篇 |
1994年 | 31篇 |
1993年 | 28篇 |
1992年 | 53篇 |
1991年 | 44篇 |
1990年 | 33篇 |
1989年 | 41篇 |
1988年 | 41篇 |
1987年 | 40篇 |
1986年 | 39篇 |
1985年 | 29篇 |
1984年 | 28篇 |
1983年 | 23篇 |
1982年 | 22篇 |
1981年 | 22篇 |
1980年 | 20篇 |
1979年 | 21篇 |
1977年 | 14篇 |
1976年 | 11篇 |
1975年 | 25篇 |
1974年 | 19篇 |
1973年 | 14篇 |
排序方式: 共有10000条查询结果,搜索用时 11 毫秒
71.
Many microbial pathogens subvert cell surface heparan sulfate proteoglycans (HSPGs) to infect host cells in vitro. The significance of HSPG-pathogen interactions in vivo, however, remains to be determined. In this study, we examined the role of syndecan-1, a major cell surface HSPG of epithelial cells, in Staphylococcus aureus corneal infection. We found that syndecan-1 null (Sdc1(-/-)) mice significantly resist S. aureus corneal infection compared with wild type (WT) mice that express abundant syndecan-1 in their corneal epithelium. However, syndecan-1 did not bind to S. aureus, and syndecan-1 was not required for the colonization of cultured corneal epithelial cells by S. aureus, suggesting that syndecan-1 does not mediate S. aureus attachment to corneal tissues in vivo. Instead, S. aureus induced the shedding of syndecan-1 ectodomains from the surface of corneal epithelial cells. Topical administration of purified syndecan-1 ectodomains or heparan sulfate (HS) significantly increased, whereas inhibition of syndecan-1 shedding significantly decreased the bacterial burden in corneal tissues. Furthermore, depletion of neutrophils in the resistant Sdc1(-/-) mice increased the corneal bacterial burden to that of the susceptible WT mice, suggesting that syndecan-1 moderates neutrophils to promote infection. We found that syndecan-1 does not affect the infiltration of neutrophils into the infected cornea but that purified syndecan-1 ectodomain and HS significantly inhibit neutrophil-mediated killing of S. aureus. These data suggest a previously unknown bacterial subversion mechanism where S. aureus exploits the capacity of syndecan-1 ectodomains to inhibit neutrophil-mediated bacterial killing mechanisms in an HS-dependent manner to promote its pathogenesis in the cornea. 相似文献
72.
Efficiency Enhancement of Organic Solar Cells Using Hydrophobic Antireflective Inverted Moth‐Eye Nanopatterned PDMS Films 下载免费PDF全文
Jung Woo Leem Sehwan Kim Soo Hyun Lee John A. Rogers Eunkyoung Kim Jae Su Yu 《Liver Transplantation》2014,4(8)
Poly‐dimethylsiloxane (PDMS) films with 2D periodic inverted moth‐eye nanopatterns on one surface are implemented as antireflection (AR) layers on a glass substrate for efficient light capture in encapsulated organic solar cells (OSCs). The inverted moth‐eye nanopatterned PDMS (IMN PDMS) films are fabricated by a soft imprint lithographic method using conical subwavelength grating patterns formed by laser interference lithography/dry etching. Their optical characteristics, together with theoretical analysis using rigorous coupled‐wave analysis simulation, and wetting behaviors are investigated. For a period of 380 nm, IMN PDMS films laminated on glass substrates exhibit a hydrophobic surface with a water contact angle (θCA) of ≈120° and solar weighted transmittance (SWT) of ≈94.2%, both significantly higher than those (θCA≈ 36° and SWT ≈ 90.3%) of bare glass substrates. By employing IMN PDMS films with a period of 380 nm on glass substrates for OSCs, an enhanced power conversion efficiency (PCE) of 6.19% is obtained mainly due to the increased short‐circuit current density (Jsc) of 19.74 mA cm‐2 compared to the OSCs with the bare glass substrates (PCE = 5.16% and Jsc = 17.25 mA cm‐2). For the OSCs, the device stability is also studied. 相似文献
73.
Seong Jin Jeong Han Sol Lee Jeong Keun Lee Jin Woo Jeong Sang Cheol Lee Jeong Hyun Kim Sung Kyu Hong Seok-Soo Byun Sang Eun Lee 《PloS one》2014,9(11)
Objectives
Mid-urethral sling (MUS) surgery for the treatment of urinary incontinence has been widespread since the introduction of tension-free vaginal tape in the mid-1990s. The majority of studies with short-term follow-up <2 years found no differences in the surgical outcomes according to body mass index (BMI). However, considering the chronic influence of obesity on pelvic floor musculature, it is cautiously speculated that higher BMI could increase stress on pelvic floor and sub-urethral tape, possibly decreasing the long-term success rate in the obese population. We aimed to compare the long-term effects of BMI on the outcomes of MUS between women with retropubic and transobturator approaches.Methods
We performed a retrospective analysis on 243 consecutive women who received MUS and were followed up for ≥36 months. The influence of BMI on the success rates was separately estimated and the factors for treatment failure were examined using logistic regression in either approach.Results
The mean follow-up was 58.4 months, and 30.5% were normal weight, 51.0% overweight, and 18.5% obese. Patients received either the retropubic (30.5%) or transobturator (69.5%) approach. The success rates (%) under the transobturator approach differed according to the BMI groups (94.3, 88.6, and 78.6, respectively; P = 0.037) while those under the retropubic approach were not different according to the BMI groups. However, in multivariate models, only the presence of preoperative mixed urinary incontinence (MUI) was proven to be the risk factor for treatment failure in the transobturator approach (OR 6.39, P = 0.003). The percent of subjects with MUI was higher in obese women than in non-obese women with the transobturator approach.Conclusions
BMI was not independently associated with failures in either approach. Higher success rates in women with lower BMI in the transobturator approach were attributed to the lower percent of preoperative MUI in those with lower BMI. 相似文献74.
Kyung-Ha Ryu So-Yeon Kim Ye-Ryung Kim So-Youn Woo Sun Hee Sung Han Su Kim Sung-Chul Jung Inho Jo Joo-Won Park 《Experimental cell research》2014
Acute liver failure, the fatal deterioration of liver function, is the most common indication for emergency liver transplantation, and drug-induced liver injury and viral hepatitis are frequent in young adults. Stem cell therapy has come into the limelight as a potential therapeutic approach for various diseases, including liver failure and cirrhosis. In this study, we investigated therapeutic effects of tonsil-derived mesenchymal stem cells (T-MSCs) in concanavalin A (ConA)- and acetaminophen-induced acute liver injury. ConA-induced hepatitis resembles viral and immune-mediated hepatic injury, and acetaminophen overdose is the most frequent cause of acute liver failure in the United States and Europe. Intravenous administration of T-MSCs significantly reduced ConA-induced hepatic toxicity, but not acetaminophen-induced liver injury, affirming the immunoregulatory capacity of T-MSCs. T-MSCs were successfully recruited to damaged liver and suppressed inflammatory cytokine secretion. T-MSCs expressed high levels of galectin-1 and -3, and galectin-1 knockdown which partially diminished interleukin-2 and tumor necrosis factor α secretion from cultured T-cells. Galectin-1 knockdown in T-MSCs also reversed the protective effect of T-MSCs on ConA-induced hepatitis. These results suggest that galectin-1 plays an important role in immunoregulation of T-MSCs, which contributes to their protective effect in immune-mediated hepatitis. Further, suppression of T-cell activation by frozen and thawed T-MSCs implies great potential of T-MSC banking for clinical utilization in immune-mediated disease. 相似文献
75.
M. Matzapetakis M. Dakanali C. P. Raptopoulou V. Tangoulis A. Terzis N. Moon J. Giapintzakis A. Salifoglou 《Journal of biological inorganic chemistry》2000,5(4):469-474
Citric acid represents a class of carboxylic acids present in biological fluids and playing key roles in biochemical processes in bacteria and humans. Its ability to promote diverse coordination chemistries in aqueous media, in the presence of metal ions known to act as trace elements in human metabolism, earmarks its involvement in a number of physiological functions. Cobalt is known to be a central element of metabolically important biomolecules, such as B12, and therefore its biospeciation in biological fluids constitutes a theme worthy of chemical and biological perusal. In an effort to unravel the aqueous chemistry of cobalt in the presence of a physiologically relevant ligand, citrate, the first aqueous, soluble, mononuclear complex has been synthesized and isolated from reaction mixtures containing Co(II) and citrate in a 1:2 molar ratio at pH approximately 8. The crystalline compound (NH4)4[Co(C6H5O7)2] (1) has been characterized spectroscopically (UV/vis, EPR) and crystallographically. Its X-ray structure consists of a distorted octahedral anion with two citrate ligands fulfilling the coordination requirements of the Co(II) ion. The magnetic susceptibility measurements of 1 in the range from 6 to 295 K are consistent with a high-spin complex containing Co(II) with a ground state S=3/2. Corroborating this result is the EPR spectrum of 1, which shows a signal consistent with the presence of a Co(II) system. The spectroscopic and structural properties of the complex signify its potential biological relevance and participation in speciation patterns arising under conditions consistent with those employed for its synthesis and isolation. 相似文献
76.
Hee Jung Lim Jusong Kim Chang-Hwan Park Sang A. Lee Man Ryul Lee Kye-Seong Kim Jaesang Kim Yun Soo Bae 《The Journal of biological chemistry》2016,291(2):752-761
We have previously reported that Ahnak-mediated TGFβ signaling leads to down-regulation of c-Myc expression. Here, we show that inhibition of Ahnak can promote generation of induced pluripotent stem cells (iPSC) via up-regulation of endogenous c-Myc. Consistent with the c-Myc inhibitory role of Ahnak, mouse embryonic fibroblasts from Ahnak-deficient mouse (Ahnak−/− MEF) show an increased level of c-Myc expression compared with wild type MEF. Generation of iPSC with just three of the four Yamanaka factors, Oct4, Sox2, and Klf4 (hereafter 3F), was significantly enhanced in Ahnak−/− MEF. Similar results were obtained when Ahnak-specific shRNA was applied to wild type MEF. Of note, expressionof Ahnak was significantly induced during the formation of embryoid bodies from embryonic stem cells, suggesting that Ahnak-mediated c-Myc inhibition is involved in embryoid body formation and the initial differentiation of pluripotent stem cells. The iPSC from 3F-infected Ahnak−/− MEF cells (Ahnak−/−-iPSC-3F) showed expression of all stem cell markers examined and the capability to form three primary germ layers. Moreover, injection of Ahnak−/−-iPSC-3F into athymic nude mice led to development of teratoma containing tissues from all three primary germ layers, indicating that iPSC from Ahnak−/− MEF are bona fide pluripotent stem cells. Taken together, these data provide evidence for a new role for Ahnak in cell fate determination during development and suggest that manipulation of Ahnak and the associated signaling pathway may provide a means to regulate iPSC generation. 相似文献
77.
78.
Cadman CJ Lopper M Moon PB Keck JL McGlynn P 《The Journal of biological chemistry》2005,280(48):39693-39700
The frequency with which replication forks break down in all organisms requires that specific mechanisms ensure completion of genome duplication. In Escherichia coli a major pathway for reloading of the replicative apparatus at sites of fork breakdown is dependent on PriA helicase. PriA acts in conjunction with PriB and DnaT to effect loading of the replicative helicase DnaB back onto the lagging strand template, either at stalled fork structures or at recombination intermediates. Here we showed that PriB stimulates PriA helicase, acting to increase the apparent processivity of PriA. This stimulation correlates with the ability of PriB to form a ternary complex with PriA and DNA structures containing single-stranded DNA, suggesting that the known single-stranded DNA binding function of PriB facilitates unwinding by PriA helicase. This enhanced apparent processivity of PriA might play an important role in generating single-stranded DNA at stalled replication forks upon which to load DnaB. However, stimulation of PriA by PriB is not DNA structure-specific, demonstrating that targeting of stalled forks and recombination intermediates during replication restart likely resides with PriA alone. 相似文献
79.
The present study explores the dietary effect of pectin on the MLN lymphocyte functions of mice with dextran sulfate sodium (DS)-induced colitis. We found that the immunoglobulin (Ig)A level in mesenteric lymph node (MLN) lymphocytes was high, while the IgE level was lower, in mice fed with pectin than in those fed with cellulose. Interestingly, the fecal IgA concentration of the pectin-fed mice was significantly higher than that of the cellulose-fed mice. The concentrations of interferon-gamma and interleukin (IL)-2 treated with concanavalin A (ConA) were significantly higher in the pectin-fed group than in the cellulose-fed group. Although dietary pectin did not affect the IL-4 and IL-10 levels, the activation-induced IL-4 and IL-10 secretion was lower in MLN cells of the pectin-fed mice than of the cellulose-fed mice following DS-induced colitis. Based on these findings, we propose that the effect of dietary pectin on mice with DS-induced colitis is mediated by the manipulation of Th1 cells. Furthermore, the inhibitory effect of IL-4 and IL-10 by dietary pectin may play an important role in promoting a change in Th1/Th2 balance toward Th1-dominant immunity. 相似文献
80.
Summary Both the fast and slow muscle fibres of advanced teleost fish are multiply innervated. The fraction of slow-fibre volume occupied by mitochondria is 31.3%, 25.5% and 24.6%, respectively, for the myotomal muscles of brook trout (Salvelinus fontinalis), crucian carp (Carassius carassius), and plaice (Pleuronectes platessa), respectively. The corresponding figures for the fast muscles of these species are 9.3%, 4.6% and 2.0%, respectively. Cytochrome-oxidase and citrate-synthetase activities in the fast muscles of 9 species of teleost range from 0.20–0.93 moles substrate utilised, g wet weight muscle-1 min-1 (at 15° C) or around 4–17% of that of the corresponding slow fibres. Ultrastructural analyses reveal a marked heterogeneity within the fast-fibre population. For example, the fraction of fibres with <1% or >10% mitochondria is 0,4,42% and 36, 12 and 0%, respectively, for trout, carp and plaice. In general, small fibres (<500 m2) have the highest and large fibres (>1,500 m2) the lowest mitochondrial densities. The complexity of mitochondrial cristae is reduced in fast compared to slow fibres.Hexokinase activities range from 0.4–2.5 in slow and from 0.08–0.7 moles, g wet weight-1 min-1 in fast muscles, indicating a wide variation in their capacity for aerobic glucose utilisation. Phosphofructokinase activities are 1.2 to 3.6 times higher in fast than slow muscles indicating a greater glycolytic potential. Lactate dehydrogenase activities are not correlated with either the predicted anaerobic scopes for activity or the anoxic tolerances of the species studied. The results indicate a considerable variation in the aerobic capacities and principal fuels supporting activity among the fast muscles of different species. Brook trout and crucian carp are known to recruit fast fibres at low swimming speeds. For these species the aerobic potential of the fast muscle is probably sufficient to meet the energy requirements of slow swimming. 相似文献