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   19620篇
  免费   1334篇
  国内免费   1243篇
  22197篇
  2024年   141篇
  2023年   282篇
  2022年   544篇
  2021年   901篇
  2020年   645篇
  2019年   705篇
  2018年   727篇
  2017年   545篇
  2016年   705篇
  2015年   1147篇
  2014年   1264篇
  2013年   1365篇
  2012年   1561篇
  2011年   1498篇
  2010年   980篇
  2009年   833篇
  2008年   905篇
  2007年   875篇
  2006年   770篇
  2005年   656篇
  2004年   617篇
  2003年   543篇
  2002年   515篇
  2001年   393篇
  2000年   390篇
  1999年   359篇
  1998年   168篇
  1997年   161篇
  1996年   158篇
  1995年   119篇
  1994年   146篇
  1993年   90篇
  1992年   155篇
  1991年   147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
181.
贵州大方喀斯特区领春木群落特征研究   总被引:2,自引:0,他引:2  
采用植物群落学研究方法,对典型喀斯特区大方福建柏自然保护区内领春木(Euptelea pleiospermum)群落进行了研究。结果表明:群落植物种类丰富,科属组成极为分散,区系成分复杂。科级地理成分热带性质较强(45.28%),属级地理成分以温带性质为主(39.44%)。群落外貌以中、小型叶面积、单叶、落叶草质、革质、非全缘的高位芽植物组成为特征。垂直结构复杂,成层现象明显,可分为乔木层、灌木层、草本层和地被层,并有一定层间植物伴生。乔木层、灌木层、草本层的Shannon-Wiener指数分别为2.5561、2.6954、1.9145。  相似文献   
182.
The porous properties of brain tissue are important for understanding normal and abnormal cerebrospinal fluid flow in the brain. In this study, a poroviscoelastic model was fitted to the stress relaxation response of white matter in unconfined compression performed under a range of low strain rates. A set of experiments was also performed on the tissue samples using a no-slip boundary condition. Results from these experiments demonstrated that the rheological response of the white matter is primarily governed by the intrinsic viscoelastic properties of the solid phase. The permeability of white matter was found to be of the order of 10(-12) m4/Ns.  相似文献   
183.
184.
Molecular tagging and mapping of the erect panicle gene in rice   总被引:6,自引:0,他引:6  
Erect panicle (EP) is one of the more important traits of the proposed ideotype of high-yielding rice. Several rice cultivars with the EP phenotype, which has been reported to be controlled by a dominant gene, have been successfully developed and released for commercial production in North China. To analyze the inheritance of the EP trait, we generated segregating F2 and BC1F1 populations by crossing an EP-type variety, Liaojing 5, and a curved-panicle-type variety, Fengjin. Our results confirmed that a dominant gene controls the EP trait. Simple-sequence repeat (SSR) and bulked segregant analyses of the F2 population revealed that the EP gene is located on chromosome 9, between two newly developed SSR markers, RM5833-11 and RM5686-23, at a genetic distance of 1.5 and 0.9 cM, respectively. Markers closer to the EP gene were developed by amplified fragment length polymorphism (AFLP) analysis with 128 AFLP primer combinations. Three AFLP markers were found to be linked to the EP gene, and the nearest marker, E-TA/M-CTC200, was mapped to the same location as SSR marker RM5686-23, 1.5 cM from the EP gene. A local map around the EP gene comprising nine SSR and one AFLP marker was constructed. These markers will be useful for marker-assisted selection (MAS) for the EP trait in rice breeding programs.  相似文献   
185.
186.
Immune response-related genes play a major role in colorectal carcinogenesis by mediating inflammation or immune-surveillance evasion. Although remarkable progress has been made to investigate the underlying mechanism, the understanding of the complicated carcinogenesis process was enormously hindered by large-scale tumor heterogeneity. Development and carcinogenesis share striking similarities in their cellular behavior and underlying molecular mechanisms. The association between embryonic development and carcinogenesis makes embryonic development a viable reference model for studying cancer thereby circumventing the potentially misleading complexity of tumor heterogeneity. Here we proposed that the immune genes, responsible for intra-immune cooperativity disorientation (defined in this study as disruption of developmental expression correlation patterns during carcinogenesis), probably contain untapped prognostic resource of colorectal cancer. In this study, we determined the mRNA expression profile of 137 human biopsy samples, including samples from different stages of human colonic development, colorectal precancerous progression and colorectal cancer samples, among which 60 were also used to generate miRNA expression profile. We originally established Spearman correlation transition model to quantify the cooperativity disorientation associated with the transition from normal to precancerous to cancer tissue, in conjunction with miRNA-mRNA regulatory network and machine learning algorithm to identify genes with prognostic value. Finally, a 12-gene signature was extracted, whose prognostic value was evaluated using Kaplan–Meier survival analysis in five independent datasets. Using the log-rank test, the 12-gene signature was closely related to overall survival in four datasets (GSE17536, n = 177, p = 0.0054; GSE17537, n = 55, p = 0.0039; GSE39582, n = 562, p = 0.13; GSE39084, n = 70, p = 0.11), and significantly associated with disease-free survival in four datasets (GSE17536, n = 177, p = 0.0018; GSE17537, n = 55, p = 0.016; GSE39582, n = 557, p = 4.4e-05; GSE14333, n = 226, p = 0.032). Cox regression analysis confirmed that the 12-gene signature was an independent factor in predicting colorectal cancer patient’s overall survival (hazard ratio: 1.759; 95% confidence interval: 1.126–2.746; p = 0.013], as well as disease-free survival (hazard ratio: 2.116; 95% confidence interval: 1.324–3.380; p = 0.002).  相似文献   
187.
Ovarian high-grade serous carcinomas (HGSCs) and invasive low-grade serous carcinomas (LGSCs) are considered to be distinct entities. In particular, LGSCs are thought to arise from non-invasive serous borderline ovarian tumors (SBOTs) and show poor responsiveness to conventional chemotherapy. The pro-apoptotic effects of CD40 ligand (CD40L) have been demonstrated in HGSC, though the underlying mechanisms are not fully understood. Conversely, the therapeutic potential of the CD40L-CD40 system has yet to be evaluated in LGSC. We now show that CD40 protein is focally expressed on tumor cells in two of five primary LGSCs compared with no expression in eight primary SBOTs. Treatment with CD40L or agonistic CD40 antibody decreased the viability of LGSC-derived MPSC1 and VOA1312 cells, but not SBOT3.1 cells. Small interfering RNA (siRNA) targeting CD40 was used to show that it is required for these reductions in cell viability. CD40L treatment increased cleaved caspase-3 levels in MPSC1 cells though, surprisingly, neither pan-caspase inhibitor nor caspase-3 siRNA reversed or even attenuated CD40L-induced cell death. In addition, CD40-induced cell death was not affected by knockdown of the mitochondrial proteins apoptosis-inducing factor (AIF) and endonuclease G (EndoG). Interestingly, CD40L-induced cell death was blocked by necrostatin-1, an inhibitor of receptor-interacting protein 1 (RIP1), and attenuated by inhibitors of RIP3 (GSK''872) or MLKL (mixed lineage kinase domain-like; necrosulfonamide). Our results indicate that the upregulation of CD40 may be relatively common in LGSC and that CD40 activation induces RIP1-dependent, necroptosis-like cell death in LGSC cells.Epithelial ovarian cancer accounts for approximately 90% of all ovarian malignancies and is the leading cause of gynecological cancer death in developed countries.1, 2 Recently, differences in molecular alterations and clinicopathological features have established a dualistic model dividing ovarian serous carcinomas into high-grade serous carcinoma (HGSC) and low-grade serous carcinoma (LGSC) subtypes. HGSCs are more common and are thought to develop directly from the ovarian surface epithelium or from serous tubal intra-epithelial carcinomas in the fallopian tube. In contrast, LGSCs are rare and are generally considered to develop from benign serous cystadenomas through serous borderline ovarian tumors (SBOT). SBOTs are slow-growing, non-invasive epithelial neoplasms that have a better prognosis compared with other types of ovarian cancer.3, 4, 5 Our previous studies have shown that the inhibition of p53 or treatment of epidermal growth factor or transforming growth factor-β1 increases SBOT cell invasion by inducing epithelial–mesenchymal transition, which suggests a possible mechanism that mediates the progression from SBOT to LGSC.6, 7, 8, 9 However, many of SBOTs recur as LGSCs that display poor responsiveness to conventional chemotherapy and for which survival rates are <50%.1, 3, 10 Thus, the development of novel, targeted therapeutic strategies is likely required to significantly improve patient survival.CD40, a transmembrane glycoprotein belonging to the tumor necrosis factor receptor superfamily, is expressed by a wide range of cell types including immune, endothelial and epithelial cells. Engagement of CD40 with its ligand, CD40L, has been shown to have important roles in a variety of physiological and pathological processes, especially in immunity.11, 12 In addition, CD40 expression has been demonstrated in several types of cancer, including colon, lung, cervical, bladder and prostate cancer.13 However, reported functions of CD40 in tumor cells vary, with both pro-apoptotic and anti-proliferative effects observed depending on the cellular context.14, 15, 16 Alternatively, some studies have shown that CD40 activation may promote the neoplastic transformation and growth of normal cells.17, 18, 19 Expression of CD40 has been demonstrated in ovarian cancer cell lines and tumor samples, but not in normal ovarian tissue, suggesting that CD40 may have an important role in ovarian tumors.20, 21, 22, 23, 24 Indeed, CD40L-CD40 signaling has been shown to induce growth-inhibitory effects in HGSC cells,20, 21, 23, 24, 25 however, the therapeutic potential of CD40 in LGSC and SBOT has not been evaluated.In the present study, we report for the first time elevated CD40 expression in a significant proportion of LGSCs compared with SBOTs. Moreover, CD40 expression is elevated in LGSC-derived MPSC1 and VOA1312 cells compared with SBOT3.1 cells, and CD40 activation induces cell death via CD40 only in LGSC-derived cells. Neither pan-caspase inhibitor nor caspase-3 small interfering RNA (siRNA) has any effect on CD40L-induced MPSC1 cell death. Moreover, CD40L-induced cell death was unaffected by individual or combined knockdown of the mitochondrial proteins apoptosis-inducing factor (AIF) and endonuclease G (EndoG). Interestingly, our results suggest that receptor-interacting protein 1 (RIP1), RIP3 and MLKL are involved in CD40-induced MPSC1 cell death. These results demonstrate that CD40 induces RIP1-dependent, necroptosis-like cell death in LGSC cells.  相似文献   
188.
189.
Influenza virus vaccine (IVV) is a promising research domain that is closely related to global health matters, which has been acknowledged not only by scientists and technology developers, but also by policy-makers. Meanwhile, patents encompass valuable technological information and reflect the latest technological inventions as well as the innovative capability of a nation. However, little research has examined this up-and-coming research field using patent bibliometric method. Thus, this paper (a) designs the technology classification system and search strategy for the identification of IVV; and (b) presents a longitudinal analysis of the global IVV development based on the European Patent Office (EPO) patents. Bibliometric analysis is used to rank countries, institutions, inventors and technology subfields contributing to IVV technical progress. The results show that the global trends of IVV are a multi-developing feature of variety but an uneven technical resource distribution. Although the synthetic peptide vaccine is a comparatively young field, it already demonstrates the powerful vitality and the enormous development space. With the worldwide competition increasing, all nations especially China should be looking to increase devotion, enhance capability and regard effectiveness of technological innovation.  相似文献   
190.
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