全文获取类型
收费全文 | 4152篇 |
免费 | 319篇 |
国内免费 | 74篇 |
出版年
2024年 | 6篇 |
2023年 | 68篇 |
2022年 | 103篇 |
2021年 | 175篇 |
2020年 | 138篇 |
2019年 | 198篇 |
2018年 | 159篇 |
2017年 | 127篇 |
2016年 | 113篇 |
2015年 | 178篇 |
2014年 | 295篇 |
2013年 | 375篇 |
2012年 | 264篇 |
2011年 | 398篇 |
2010年 | 244篇 |
2009年 | 167篇 |
2008年 | 197篇 |
2007年 | 187篇 |
2006年 | 185篇 |
2005年 | 142篇 |
2004年 | 139篇 |
2003年 | 102篇 |
2002年 | 58篇 |
2001年 | 45篇 |
2000年 | 53篇 |
1999年 | 50篇 |
1998年 | 53篇 |
1997年 | 38篇 |
1996年 | 48篇 |
1995年 | 49篇 |
1994年 | 41篇 |
1993年 | 25篇 |
1992年 | 21篇 |
1991年 | 17篇 |
1990年 | 7篇 |
1989年 | 8篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1986年 | 4篇 |
1985年 | 9篇 |
1984年 | 19篇 |
1983年 | 9篇 |
1982年 | 9篇 |
1981年 | 4篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有4545条查询结果,搜索用时 15 毫秒
71.
《Journal of Asia》2020,23(2):350-357
Acridids are highly abundant living-organism/major-component in agricultural field, globally. It may act as a dependable bio-indicator species in response to environmental-stress. Antioxidants protect insects by scavenging free radicals. Here, we investigated the dose dependant azadirachtin (C35H44O16 AZT) toxicity on oxidative-biomarker; Alkaline-phosphatase (ALP), malondialdehyde (MDA), non-protein-soluble-thiol (NPSH) and antioxidants like superoxide-dismutase (SOD), catalase (CAT), glutathione-peroxidase (GPx) and amylase of gonads from both sexes and juvenile tissues of common grasshopper, Spathosternum prasiniferum prasiniferum (Walker, 1871). The newly hatched adults (female: male = 1:1) are exposed to 1 to 20 ppm AZT for 48 h and have compared to control and 6 h incubation with same concentration of azadirachtin for in vitro experiments. Both in vivo and in vitro experiment demonstrated significant influences on oxidative biomarkers with increasing antioxidant enzymatic activities in either sex. The male gonads represents decreasing antioxidant enzyme activities compared to female gonads. Lesser protection by CAT and SOD are noticed in male than female in response to AZT exposure. This experiment suggests that azadirachtin increased the major biomarkers with decreasing antioxidant enzyme activities resulting in more free-radicals related threat in adult male gonads. Variable dose responses were noticed on ALP, AchE and MDA in either gender suggesting multiphasic action of the pesticides. Higher mortality rate is noticed in male with lower nymphal life span. Moreover, nymph IInd is more susceptible than nymph IVth in vitro intoxication of azadirachtin. Possible life threat of vast representatives of agricultural ecosystem by pesticide should be avoided to maintain different bio-geo cycle and eco-sustainability. 相似文献
72.
Patricia M. LoRusso Kurt Schalper Jeffrey Sosman 《Pigment cell & melanoma research》2020,33(3):390-402
Targeted therapy directed against oncogenic BRAF mutations and immune checkpoint inhibitors have transformed melanoma therapy over the past decade and prominently improved patient outcomes. However, not all patients will respond to targeted therapy or immunotherapy and many relapse after initially responding to treatment. This unmet need presents two major challenges. First, can we elucidate novel oncogenic drivers to provide new therapeutic targets? Second, can we identify patients who are most likely to respond to current therapeutic strategies in order to both more accurately select populations and avoid undue drug exposure in patients unlikely to respond? In an effort to evaluate the current state of the field with respect to these questions, we provide an overview of some common oncogenic mutations in patients with metastatic melanoma and ongoing efforts to therapeutically target these populations, as well as a discussion of biomarkers for response to immune checkpoint inhibitors—including tumor programmed death ligand 1 expression and the future use of neoantigens as a means of truly personalized therapy. This information is becoming important in treatment decision making and provides the framework for a treatment algorithm based on the current landscape in metastatic melanoma. 相似文献
73.
Sepsis is the major cause of mortality in the intensive care unit. The aim of this study was to identify the key prognostic biomarkers of abnormal expression and immune infiltration in sepsis. In this study, a total of 36 differentially expressed genes were identified to be mainly involved in a number of immune-related Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. The hub genes (MMP9 and C3AR1) were significantly related to the prognosis of sepsis patients. The immune infiltration analysis indicated a significant difference in the relative cell content of naive B cells, follicular Th cells, activated NK cells, eosinophils, neutrophils and monocytes between sepsis and normal controls. Weighted gene co-expression network analysis and a de-convolution algorithm that quantifies the cellular composition of immune cells were used to analyse the sepsis expression data from the Gene Expression Omnibus database and to identify modules related to differential immune cells. CEBPB is the key immune-related gene that may be involved in sepsis. Gene set enrichment analysis revealed that CEBPB is involved in the processes of T cell selection, B cell–mediated immunity, NK cell activation and pathways of T cells, B cells and NK cells. Therefore, CEBPB may play a key role in the biological and immunological processes of sepsis. 相似文献
74.
《Bioorganic & medicinal chemistry letters》2020,30(17):127396
Targeting the SMAD3 protein is an attractive therapeutic strategy for treating cancer, as it avoids the potential toxicities due to targeting the TGF-β signaling pathway upstream. Compound SIS3 was the first selective SMAD3 inhibitor developed that had acceptable activity, but its poor water solubility limited its development. Here, a series of SIS3 analogs was created to investigate the structure–activity relationship for inhibiting the activation of SMAD3. On the basis of this SAR, further optimization generated a water-soluble compound, 16d, which was capable of effectively blocking SMAD3 activation in vitro and had similar NK cell-mediated anticancer effects in vivo to its parent SIS3. This study not only provided a preferable lead compound, 16d, for further drug discovery or a potential tool to study SMAD3 biology, but also proved the effectiveness of our strategy for water-solubility driven optimization. 相似文献
75.
76.
Mihaela Gheorghiu 《Asia-Pacific Journal of Blood Types and Genes》2020,4(1):19-30
Carbonic anhydrases were first identified in red blood cells and have been thus traditionally addressed in a hematological context. However, recently there has been a shift of research interest to therapeutic areas, notably in solid cancers, relegating the impact of carbonic anhydrase function and pathological dysfunction in blood related physiology to secondary importance. This review addresses this paradigm and emphasizes the potential impact of recent studies on blood related carbonic anhydrase isotype expression and modulation in diverse areas such as physiology and pathology, biosensing, their use as biomarkers, and in the development of synthetic blood. A special emphasis is placed on reviewing new dynamic and quantitative studies that allow for the efficient tracking and quantitation of various carbonic anhydrase isozymes within the blood and more generally within the human body, that give new perspectives on the biochemical and physiological role of blood associated carbonic anhydrase in health and pathology. 相似文献
77.
Purpose: Cervical cancer (CC) is one of the most general gynecological malignancies and is associated with high morbidity and mortality. We aimed to select candidate genes related to the diagnosis and prognosis of CC.Methods: The mRNA expression profile datasets were downloaded. We also downloaded RNA-sequencing gene expression data and related clinical materials from TCGA, which included 307 CC samples and 3 normal samples. Differentially expressed genes (DEGs) were obtained by R software. GO function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were performed in the DAVID dataset. Using machine learning, the optimal diagnostic mRNA biomarkers for CC were identified. We used qRT-PCR and Human Protein Atlas (HPA) database to exhibit the differences in gene and protein levels of candidate genes.Results: A total of 313 DEGs were screened from the microarray expression profile datasets. DNA methyltransferase 1 (DNMT1), Chromatin Assembly Factor 1, subunit B (CHAF1B), Chromatin Assembly Factor 1, subunit A (CHAF1A), MCM2, CDKN2A were identified as optimal diagnostic mRNA biomarkers for CC. Additionally, the GEPIA database showed that the DNMT1, CHAF1B, CHAF1A, MCM2 and CDKN2A were associated with the poor survival of CC patients. HPA database and qRT-PCR confirmed that these genes were highly expressed in CC tissues.Conclusion: The present study identified five DEmRNAs, including DNMT1, CHAF1B, CHAF1A, MCM2 and Kinetochore-related protein 1 (KNTC1), as potential diagnostic and prognostic biomarkers of CC. 相似文献
78.
Acute coronary syndrome (ACS) results from inadequate supply of blood flow from the coronary arteries to the heart or ischemia. ACS has an extremely high morbidity and mortality. The levels of biomarkers currently used for detection of ACS also increase in response to myocardial necrosis and other diseases and are not elevated immediately after symptoms appear, thus limiting their diagnostic capacity. Therefore, we aimed to discover new ACS diagnostic biomarkers with high sensitivity and specificity that are specifically related to ACS pathogenesis. Sera from 50 patients with ACS and healthy controls (discovery cohort) each were analyzed using mass spectrometry (MS) to identify differentially expressed proteins, and protein candidates were evaluated as ACS biomarkers in 120 people in each group (validation cohort). α-1-acid glycoprotein 1 (AGP1), complement C5 (C5), leucine-rich α-2-glycoprotein (LRG), and vitronectin (VN) were identified as biomarkers whose levels increase and gelsolin (GSN) as a biomarker whose levels decrease in patients with ACS. We concluded that these biomarkers are associated with the pathogenesis of ACS and can predict the onset of ACS prior to the appearance of necrotic biomarkers. 相似文献
79.