首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   3102篇
  免费   335篇
  国内免费   1篇
  2021年   42篇
  2020年   38篇
  2019年   52篇
  2018年   75篇
  2017年   64篇
  2016年   93篇
  2015年   184篇
  2014年   156篇
  2013年   206篇
  2012年   245篇
  2011年   240篇
  2010年   185篇
  2009年   138篇
  2008年   146篇
  2007年   159篇
  2006年   142篇
  2005年   139篇
  2004年   171篇
  2003年   128篇
  2002年   133篇
  2001年   72篇
  2000年   60篇
  1999年   53篇
  1998年   37篇
  1997年   27篇
  1996年   24篇
  1995年   24篇
  1994年   19篇
  1993年   19篇
  1992年   22篇
  1991年   30篇
  1990年   22篇
  1989年   28篇
  1988年   21篇
  1987年   16篇
  1986年   21篇
  1985年   14篇
  1984年   21篇
  1983年   13篇
  1982年   11篇
  1981年   15篇
  1980年   14篇
  1979年   10篇
  1978年   13篇
  1977年   15篇
  1976年   10篇
  1975年   16篇
  1974年   8篇
  1973年   8篇
  1969年   6篇
排序方式: 共有3438条查询结果,搜索用时 15 毫秒
1.
2.
Craniofacial bone defects are observed in a variety of clinical situations, and their reconstructions require coordinated coupling between angiogenesis and osteogenesis. In this study, we explored the effects of cartilage oligomeric matrix protein-angiopoietin 1 (COMP-Ang1), a synthetic and soluble variant of angiopoietin 1, on bone morphogenetic protein 2 (BMP2)-induced cranial bone regeneration, and recruitment and osteogenic differentiation of perivascular pericytes. A critical-size calvarial defect was created in the C57BL/6 mouse and COMP-Ang1 and/or BMP2 proteins were delivered into the defects with absorbable collagen sponges. After 3 weeks, bone regeneration was evaluated using micro-computed tomography and histologic examination. Pericyte recruitment into the defects was examined using immunofluorescence staining with anti-NG2 and anti-CD31 antibodies. In vitro recruitment and osteoblastic differentiation of pericyte cells were assessed with Boyden chamber assay, staining of calcified nodules, RT-PCR and Western blot analyses. Combined administration of COMP-Ang1 and BMP2 synergistically enhanced bone repair along with the increased population of CD31 (an endothelial cell marker) and NG2 (a specific marker of pericyte) positive cells. In vitro cultures of pericytes consistently showed that pericyte infiltration into the membrane pore of Boyden chamber was more enhanced by the combination treatment. In addition, the combination further increased the osteoblast-specific gene expression, including bone sialoprotein (BSP), osteocalcin (OCN) and osterix (OSX), phosphorylation of Smad/1/5/8, and mineralized nodule formation. COMP-Ang1 can enhance BMP2-induced cranial bone regeneration with increased pericyte recruitment. Combined delivery of the proteins might be a therapeutic strategy to repair cranial bone damage.  相似文献   
3.
The latency and reactivation of Mycobacterium tuberculosis infection has been well studied. However, there have been few studies of the latency and reactivation of Mycobacterium avium complex (MAC), the most common etiological non-tuberculous Mycobacterium species next to M. tuberculosis in humans worldwide. We hypothesized that latent MAC infections can be reactivated following immunosuppression after combination chemotherapy with clarithromycin and rifampicin under experimental conditions. To this end, we employed a modified Cornell-like murine model of tuberculosis and investigated six strains consisting of two type strains and four clinical isolates of M. avium and M. intracellulare. After aerosol infection of each MAC strain, five to six mice per group were euthanized at 2, 4, 10, 18, 28 and 35 weeks post-infection, and lungs were sampled to analyze bacterial burden and histopathology. One strain of each species maintained a culture-negative state for 10 weeks after completion of 6 weeks of chemotherapy, but was reactivated after 5 weeks of immunosuppression in the lungs with dexamethasone (three out of six mice in M. avium infection) or sulfasalazine (four out of six mice in both M. avium and M. intracellulare infection). The four remaining MAC strains exhibited decreased bacterial loads in response to chemotherapy; however, they remained at detectable levels and underwent regrowth after immunosuppression. In addition, the exacerbated lung pathology demonstrated a correlation with bacterial burden after reactivation. In conclusion, our results suggest the possibility of MAC reactivation in an experimental mouse model, and experimentally demonstrate that a compromised immune status can induce reactivation and/or regrowth of MAC infection.  相似文献   
4.
Trienoic fatty acids, namely -linolenic acid and hexadecatrienoic acid, present in leaf lipids are produced by -3 fatty acid desaturases located in the endoplasmic reticulum and plastid membranes. The changes in the level of trienoic fatty acids during leaf maturation were investigated in wild-type plants of Arabidopsis thaliana (L.) Heynh. and in the fad7 mutant deficient in the activity of a plastid -3 desaturase. The levels of trienoic fatty acids increased in 26 °C- and 15 °C-grown wild-type plants with maturation of leaves. The increase in trienoic fatty acids was mainly due to galactolipids enriched in plastid membranes. In addition, the relative levels of trienoic fatty acids in major glycerolipids, including phospholipids enriched in the endoplasmic reticulum membranes, also increased with leaf maturation. By contrast, when the fad7 mutant was grown at 26 °C, the relative levels of trienoic fatty acids in individual lipids decreased with leaf maturation. The decreases in the levels of trienoic fatty acids, however, were alleviated when the fad7 mutant was grown at 15 °C. These results suggest that the plastid -3 desaturase plays a major role in increasing the levels of trienoic fatty acids with leaf maturation.Abbreviations 163 hexadecatrienoic acid - 183 -linolenic acid - DGD digalactosyldiacylglycerol - MGD monogalactosyldiacylglycerol - PC phosphatidylcholine - PE phosphatidylethanolamine - TA trienoic fatty acid - WT wild type - -3 refers to the position of the double bond from the methyl end of a fatty acid This research was supported in part by Grants-in-Aid for Scientific research (#07251214 and #06804050 to K.I.) from the Ministry of Education, Science and Culture, Japan, and by the research grant from Shorai Foundation.  相似文献   
5.
6.

Purpose

To determine the occurrence of intraoperative and postoperative complications up to three years after primary phacotrabeculectomy with intraoperative use of Mitomycin C (MMC) in primary open angle (POAG) and primary angle closure glaucoma (PACG) patients, and the effect of postoperative complications on surgical outcome.

Methods

Retrospective review of 160 consecutive patients with POAG (n = 105) and PACG (n = 55), who underwent primary phacotrabeculectomy with MMC at the National University Hospital, Singapore, from January 1, 2008 to December 31, 2010. Data was collected using a standardized form that included patient demographic information, ocular characteristics and postoperative complications, including hypotony (defined as intraocular pressure < 6 mmHg), shallow anterior chamber (AC) and hyphema.

Results

The mean age ± standard deviation (SD) of patients was 68.2 ± 8.2 years. No patient lost light perception during duration of follow-up. 77% of the postoperative complications occurred within the first month only. The commonest complications were hypotony (n = 41, 25.6%), hyphema (n = 16, 10.0%) and shallow AC (n = 16, 10.0%). Five patients (3.1%) required reoperation for their complications. Early hypotony (defined as hypotony < 30 days postoperatively) was an independent risk factor for surgical failure (hazard ratio [HR], 5.1; 95% CI, 1.6–16.2; p = 0.01). Hypotony with another complication was also a risk factor for surgical failure (p < 0.02).

Conclusions

Hypotony, hyphema and shallow AC were the commonest postoperative complications in POAG and PACG patients after phacotrabeculectomy with MMC. Most complications were transient and self-limiting. Early hypotony within the first month was a significant risk factor for surgical failure.  相似文献   
7.
A series of N-ethyl phthalimide esters 4(a-n) were synthesized and characterized by spectroscopic studies. Further, the molecular structure of majority of compounds were analysed by single crystal X-ray diffraction studies. The X-ray analysis revealed the importance of substituents on the crystal stability and molecular packing. All the synthesized compounds were tested for in vitro antioxidant activity by DPPH radical scavenging, FRAP and CUPRAC methods. Few of them have shown good antioxidant activity.  相似文献   
8.
Adoptive cellular immunotherapy using in vitro expanded CD8+ T cells shows promise for tumour immunotherapy but is limited by eventual loss of function of the transferred T cells through factors that likely include inactivation by tolerogenic dendritic cells (DC). The co-inhibitory receptor programmed death-1 (PD-1), in addition to controlling T-cell responsiveness at effector sites in malignancies and chronic viral diseases is an important modulator of dendritic cell-induced tolerance in naive T cell populations. The most potent therapeutic capacity amongst CD8+ T cells appears to lie within Tcm or Tcm-like cells but memory T cells express elevated levels of PD-1. Based on established trafficking patterns for Tcm it is likely Tcm-like cells interact with lymphoid-tissue DC that present tumour-derived antigens and may be inherently tolerogenic to develop therapeutic effector function. As little is understood of the effect of PD-1/PD-L1 blockade on Tcm-like CD8+ T cells, particularly in relation to inactivation by DC, we explored the effects of PD-1/PD-L1 blockade in a mouse model where resting DC tolerise effector and memory CD8+ T cells. Blockade of PD-1/PD-L1 promoted effector differentiation of adoptively-transferred Tcm-phenotype cells interacting with tolerising DC. In tumour-bearing mice with tolerising DC, effector activity was increased in both lymphoid tissues and the tumour-site and anti-tumour activity was promoted. Our findings suggest PD-1/PD-L1 blockade may be a useful adjunct for adoptive immunotherapy by promoting effector differentiation in the host of transferred Tcm-like cells.  相似文献   
9.
Allelic variation of the mouse pink-eyed dilution (p) gene in common laboratory strains and wild mice was examined by Southern blot and by polymerase chain reaction. In these assays the original p mutation allele found in strains SJL/J, 129/J, B10.129(21m), P/J and FS/Ei most closely matches an Asian Mus musculus allele, confirming anecdotal accounts of the Asian origin of this mutation. In contrast, the wild-type allele found in other common laboratory strains was apparently derived from Mus domesticus. Analysis of chromosome 7 loci both proximal and distal to the p locus demonstrates that strains SJL/J, 129/J, B10.129(21M), P/J and FS/Ei contain DNA segments of varying length derived from M. musculus. Strains 129/J and B10.129(21M) contain the largest segment of M. musculus-derived DNA (about 5 cM), including the loci Myod1, p, three clustered GABA(A) receptor subunit loci (Gabrg3, Gabra5 and Gabrb3), and Snrpn. The difference in the species origin of genes from this region of chromosome 7 may underlie the basis of the antigenicity of the minor histocompatibility antigen H4, defined by the strain B10.129(21M), and may account for the enhanced Myod1 activity observed in SJL/J mice.  相似文献   
10.
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号