全文获取类型
收费全文 | 2460篇 |
免费 | 218篇 |
国内免费 | 6篇 |
专业分类
2684篇 |
出版年
2022年 | 19篇 |
2021年 | 38篇 |
2020年 | 19篇 |
2019年 | 23篇 |
2018年 | 38篇 |
2017年 | 28篇 |
2016年 | 59篇 |
2015年 | 119篇 |
2014年 | 129篇 |
2013年 | 141篇 |
2012年 | 213篇 |
2011年 | 158篇 |
2010年 | 105篇 |
2009年 | 87篇 |
2008年 | 120篇 |
2007年 | 118篇 |
2006年 | 131篇 |
2005年 | 96篇 |
2004年 | 100篇 |
2003年 | 89篇 |
2002年 | 68篇 |
2001年 | 75篇 |
2000年 | 63篇 |
1999年 | 76篇 |
1998年 | 34篇 |
1997年 | 26篇 |
1996年 | 13篇 |
1995年 | 13篇 |
1994年 | 22篇 |
1993年 | 16篇 |
1992年 | 34篇 |
1991年 | 38篇 |
1990年 | 31篇 |
1989年 | 20篇 |
1988年 | 21篇 |
1987年 | 21篇 |
1986年 | 26篇 |
1985年 | 26篇 |
1984年 | 13篇 |
1983年 | 19篇 |
1982年 | 19篇 |
1981年 | 14篇 |
1980年 | 16篇 |
1979年 | 20篇 |
1978年 | 18篇 |
1977年 | 12篇 |
1976年 | 17篇 |
1975年 | 15篇 |
1973年 | 15篇 |
1972年 | 13篇 |
排序方式: 共有2684条查询结果,搜索用时 15 毫秒
971.
Chih-Yung Chiu Yu-Lin Huang Ming-Han Tsai Yu-Ling Tu Man-Chin Hua Tsung-Chieh Yao Kuo-Wei Yeh Jing-Long Huang 《PloS one》2014,9(7)
Objectives
A correct interpretation of sensitization to common allergens is critical in determining susceptibility to allergic diseases. The aim of this study was to investigate the patterns of sensitization to food and inhalant allergens, and their relation to the development of atopic diseases in early childhood.Methods
Children aged 0 through 4 years from a birth cohort in the Prediction of Allergies in Taiwanese Children (PATCH) study were enrolled. Specific IgE antibody against food and inhalant allergens were measured and their association between total serum IgE levels and atopic diseases were assessed.Results
A total of 182 children were regular followed up at clinics for a four-year follow-up period. The prevalence of food allergen sensitization increased markedly after 6 months of age, reaching up to 47% at 1.5 years of age and then declined significantly to 10% in parallel with a considerable increase in the prevalence of sensitization to inhalant allergens up to 25% at age 4. Food allergen sensitization appeared to be mainly associated with the elevation of serum total IgE levels before age 2. A combined sensitization to food and inhalant allergens had an additive effect on serum IgE levels after age 2, and was significantly associated with the risk of developing atopic diseases at age 4.Conclusions
Sensitization to food occurs early in life, in parallel with the rising prevalence of sensitization to inhalant allergens at older age. A combined sensitization to food and inhalant allergens not only has an additive increase in serum IgE antibody production but also increases the risk of developing allergic respiratory diseases in early childhood. 相似文献972.
Sarah H. Shahmoradian Mauricio R. Galiano Chengbiao Wu Shurui Chen Matthew N. Rasband William C. Mobley Wah Chiu 《Journal of visualized experiments : JoVE》2014,(84)
Neurites, both dendrites and axons, are neuronal cellular processes that enable the conduction of electrical impulses between neurons. Defining the structure of neurites is critical to understanding how these processes move materials and signals that support synaptic communication. Electron microscopy (EM) has been traditionally used to assess the ultrastructural features within neurites; however, the exposure to organic solvent during dehydration and resin embedding can distort structures. An important unmet goal is the formulation of procedures that allow for structural evaluations not impacted by such artifacts. Here, we have established a detailed and reproducible protocol for growing and flash-freezing whole neurites of different primary neurons on electron microscopy grids followed by their examination with cryo-electron tomography (cryo-ET). This technique allows for 3-D visualization of frozen, hydrated neurites at nanometer resolution, facilitating assessment of their morphological differences. Our protocol yields an unprecedented view of dorsal root ganglion (DRG) neurites, and a visualization of hippocampal neurites in their near-native state. As such, these methods create a foundation for future studies on neurites of both normal neurons and those impacted by neurological disorders. 相似文献
973.
Y-L Chen C-Y Wang F-Y Yang B-S Wang J Y Chen L-T Lin J-D Leu S-J Chiu F-D Chen Y-J Lee W R Chen 《Cell death & disease》2014,5(4):e1178
Stimulation of the host immune system is crucial in cancer treatment. In particular, nonspecific immunotherapies, when combined with other traditional therapies such as radiation and chemotherapy, may induce immunity against primary and metastatic tumors. In this study, we demonstrate that a novel, non-toxic immunoadjuvant, glycated chitosan (GC), decreases the motility and invasion of mammalian breast cancer cells in vitro and in vivo. Lung metastatic ratios were reduced in 4T1 tumor-bearing mice when intratumoral GC injection was combined with local high-intensity focused ultrasound (HIFU) treatment. We postulate that this treatment modality stimulates the host immune system to combat cancer cells, as macrophage accumulation in tumor lesions was detected after GC-HIFU treatment. In addition, plasma collected from GC-HIFU-treated tumor-bearing mice exhibited tumor-specific cytotoxicity. We also investigated the effect of GC on epithelial–mesenchymal transition-related markers. Our results showed that GC decreased the expression of Twist-1 and Slug, proto-oncogenes commonly implicated in metastasis. Epithelial-cadherin, which is regulated by these genes, was also upregulated. Taken together, our current data suggest that GC alone can reduce cancer cell motility and invasion, whereas GC-HIFU treatment can induce immune responses to suppress tumor metastasis in vivo. 相似文献
974.
Mechanisms of thrombin-induced MAPK activation associated with cell proliferation in human cultured tracheal smooth muscle cells 总被引:4,自引:0,他引:4
The elevated level of thrombin has been detected in the airway fluids of asthmatic patients. However, the implication of thrombin in the pathogenesis of bronchial hyperreactivity was not completely understood. Therefore, in this study we investigated the effect of thrombin on cell proliferation and p42/p44 mitogen-activated protein kinase (MAPK) activation in human tracheal smooth muscle cells (TSMCs). Thrombin stimulated [3H]thymidine incorporation and p42/p44 MAPK phosphorylation in a time- and concentration-dependent manner in TSMCs. Pretreatment of TSMCs with pertussis toxin (PTX) significantly inhibited [3H]thymidine incorporation and phosphorylation of MAPK induced by thrombin. These responses were attenuated by tyrosine kinase inhibitors genistein and herbimycin A, phosphatidyl inositide (PI)-phospholipase C (PLC) inhibitor U73122, protein kinase C (PKC) inhibitor GF109203X, removal of Ca(2+) by addition of BAPTA/AM plus EGTA, and PI 3-kinase inhibitors wortmannin and LY294002. In addition, thrombin-induced [3H]-thymidine incorporation and p42/p44 MAPK phosphorylation was completely inhibited by PD98059 (an inhibitor of MEK1/2), indicating that activation of MEK1/2 was required for these responses. Furthermore, overexpression of dominant negative mutants, RasN17 and Raf-301, significantly suppressed p42/p44 MAPK activation induced by thrombin and PDGF-BB, indicating that Ras and Raf may be required for activation of these kinases. These results conclude that the mitogenic effect of thrombin was mediated through the activation of Ras/Raf/MEK/MAPK pathway. Thrombin-mediated MAPK activation was modulated by PI-PLC, Ca(2+), PKC, tyrosine kinase, and PI 3-kinase associated with cell proliferation in cultured human TSMCs. 相似文献
975.
976.
977.
Deanna Lee Jaydip Das Gupta Christina Gaughan Imke Steffen Ning Tang Ka-Cheung Luk Xiaoxing Qiu Anatoly Urisman Nicole Fischer Ross Molinaro Miranda Broz Gerald Schochetman Eric A. Klein Don Ganem Joseph L. DeRisi Graham Simmons John Hackett Jr Robert H. Silverman Charles Y. Chiu 《PloS one》2012,7(9)
XMRV, or xenotropic murine leukemia virus (MLV)-related virus, is a novel gammaretrovirus originally identified in studies that analyzed tissue from prostate cancer patients in 2006 and blood from patients with chronic fatigue syndrome (CFS) in 2009. However, a large number of subsequent studies failed to confirm a link between XMRV infection and CFS or prostate cancer. On the contrary, recent evidence indicates that XMRV is a contaminant originating from the recombination of two mouse endogenous retroviruses during passaging of a prostate tumor xenograft (CWR22) in mice, generating laboratory-derived cell lines that are XMRV-infected. To confirm or refute an association between XMRV and prostate cancer, we analyzed prostate cancer tissues and plasma from a prospectively collected cohort of 39 patients as well as archival RNA and prostate tissue from the original 2006 study. Despite comprehensive microarray, PCR, FISH, and serological testing, XMRV was not detected in any of the newly collected samples or in archival tissue, although archival RNA remained XMRV-positive. Notably, archival VP62 prostate tissue, from which the prototype XMRV strain was derived, tested negative for XMRV on re-analysis. Analysis of viral genomic and human mitochondrial sequences revealed that all previously characterized XMRV strains are identical and that the archival RNA had been contaminated by an XMRV-infected laboratory cell line. These findings reveal no association between XMRV and prostate cancer, and underscore the conclusion that XMRV is not a naturally acquired human infection. 相似文献
978.
The ATM/ATR DNA damage checkpoint functions in the maintenance of genetic stability and some missense variants of the ATM gene have been shown to confer a moderate increased risk of prostate cancer. However, whether inactivation of this checkpoint contributes directly to prostate specific cancer predisposition is still unknown. Here, we show that exposure of non-malignant prostate epithelial cells (HPr-1AR) to androgen led to activation of the ATM/ATR DNA damage response and induction of cellular senescence. Notably, knockdown of the ATM gene expression in HPr-1AR cells can promote androgen-induced TMPRSS2: ERG rearrangement, a prostate-specific chromosome translocation frequently found in prostate cancer cells. Intriguingly, unlike the non-malignant prostate epithelial cells, the ATM/ATR DNA damage checkpoint appears to be defective in prostate cancer cells, since androgen treatment only induced a partial activation of the DNA damage response. This mechanism appears to preserve androgen induced autophosphorylation of ATM and phosphorylation of H2AX, lesion processing and repair pathway yet restrain ATM/CHK1/CHK2 and p53 signaling pathway. Our findings demonstrate that ATM/ATR inactivation is a crucial step in promoting androgen-induced genomic instability and prostate carcinogenesis. 相似文献
979.
Since Bechara et al. pioneered its development, the Iowa Gambling Task (IGT) has been widely applied to elucidate decision behavior and medial prefrontal function. Although most decision makers can hunch the final benefits of IGT, ventromedial prefrontal lesions generate a myopic choice pattern. Additionally, the Iowa group developed a revised IGT (inverted IGT, iIGT) to confirm the IGT validity. Each iIGT trial was generated from the trial of IGT by multiplying by a “−” to create an inverted monetary value. Thus, bad decks A and B in the IGT become good decks iA and iB in the iIGT; additionally, good decks C and D in the IGT become bad decks iC and iD in the iIGT. Furthermore, IGT possessed mostly the gain trials, and iIGT possessed mainly the loss trials. Therefore, IGT is a frequent-gain–based task, and iIGT is a frequent-loss–based task. However, a growing number of IGT-related studies have identified confounding factors in IGT (i.e., gain-loss frequency), which are demonstrated by the prominent deck B phenomenon (PDB phenomenon). Nevertheless, the mirrored PDB phenomenon and guiding power of gain-loss frequency in iIGT have seldom been reexamined. This experimental finding supports the prediction based on gain-loss frequency. This study identifies the mirrored PDB phenomenon. Frequent small losses override occasional large gains in deck iB of the iIGT. Learning curve analysis generally supports the phenomenon based on gain-loss frequency rather than final outcome. In terms of iIGT and simple versions of iIGT, results of this study demonstrate that high-frequency loss, rather than a satisfactory final outcome, dominates the preference of normal decision makers under uncertainty. Furthermore, normal subjects prefer “no immediate punishment” rather than “final reward” under uncertainty. 相似文献
980.
Hon-Yi Shi Hao-Hsien Lee Jinn-Tsong Tsai Wen-Hsien Ho Chieh-Fan Chen King-Teh Lee Chong-Chi Chiu 《PloS one》2012,7(12)