全文获取类型
收费全文 | 16482篇 |
免费 | 1430篇 |
国内免费 | 1591篇 |
出版年
2024年 | 43篇 |
2023年 | 232篇 |
2022年 | 427篇 |
2021年 | 949篇 |
2020年 | 664篇 |
2019年 | 768篇 |
2018年 | 764篇 |
2017年 | 571篇 |
2016年 | 743篇 |
2015年 | 1052篇 |
2014年 | 1290篇 |
2013年 | 1294篇 |
2012年 | 1551篇 |
2011年 | 1386篇 |
2010年 | 812篇 |
2009年 | 791篇 |
2008年 | 884篇 |
2007年 | 773篇 |
2006年 | 606篇 |
2005年 | 476篇 |
2004年 | 479篇 |
2003年 | 401篇 |
2002年 | 346篇 |
2001年 | 262篇 |
2000年 | 244篇 |
1999年 | 227篇 |
1998年 | 152篇 |
1997年 | 142篇 |
1996年 | 146篇 |
1995年 | 113篇 |
1994年 | 112篇 |
1993年 | 86篇 |
1992年 | 95篇 |
1991年 | 89篇 |
1990年 | 67篇 |
1989年 | 53篇 |
1988年 | 50篇 |
1987年 | 32篇 |
1986年 | 40篇 |
1985年 | 41篇 |
1984年 | 26篇 |
1983年 | 28篇 |
1982年 | 17篇 |
1980年 | 14篇 |
1979年 | 22篇 |
1977年 | 12篇 |
1975年 | 20篇 |
1974年 | 16篇 |
1973年 | 12篇 |
1970年 | 15篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
971.
SMAD ubiquitination regulatory factor 1 (SMURF1) has been described as a tumor suppressor in multiple aggressive cancers. Nevertheless, the potential role of SMURF1 in ovarian cancer invasion and epithelial-to-mesenchymal transition (EMT) remains unclear. The aim of this study was to evaluate the efficacy of SMURF1 on tumor migration and EMT and elucidate the underlying molecular mechanism in ovarian carcinoma. We found elevated SMURF1 in several ovarian cancer cells in both messenger RNA and protein. Additionally, silencing SMURF1 apparently repressed cell proliferation and invasion capacity of SKOV3 and A2780 cells and markedly attenuated expression of linked proteins such as proliferating cellnuclear antigen, matrix metalloproteinase (MMP)-2, and MMP-9. Furthermore, depletion of SMURF1 dramatically impeded EMT progress by modulating EMT biomarkers, with a notable increase in E-cadherin expression accompanied by the decrease in N-cadherin and vimentin in both SKOV3 and A2780 cells. Interestingly, elimination of SMURF1 led to disabled homolog 2 DOC-2/DAB2 interacting protein (DAB2IP) activation and dampened AKT/Skp2 signaling. Most important, depleted of DAB2IP or treatment with the AKT agonist 740Y-P effectively abolished the suppressive effects of SMURF1 knockout on cell invasiveness and EMT process. Taken all data together, these findings demonstrated that the absence of SMURF1 repressed cell proliferation, invasive capability, and EMT process in ovarian cancer through DAB2IP/AKT/Skp2 signaling loops, suggesting that SMURF1 may serve as a new potential therapeutic agent for ovarian cancer. 相似文献
972.
Xiuying Shi Biying Jiang Haifeng Liu Chuifeng Fan 《Journal of cellular biochemistry》2019,120(6):10596-10604
ZCCHC9 is a type of CCHC type zinc-finger containing protein which was found to be expressed in some tissues including brain and testicles in mice. Expression and function of ZCCHC9 in human tissues including cancer was largely unknown. In this study, we investigated the expression and function of ZCCHC9 in human non-small cell lung cancer (NSCLC) and the related molecular mechanism. Immunochemistrical standing showed that ZCCHC9 was mainly located in the nucleus in bronchial epithelial cells and epithelial cells of submucosal glands (58.3% [14/24]). But in NSCLC cells ZCCHC9 was mainly located in the cytoplasm and the positive rate was 54.5% (60/110). Ectopic cytoplasmic expression of ZCCHC9 in cancer tissues was significantly associated with advanced TNM stages (III+IV), lymph node metastasis, and poor clinical outcome (P < 0.05). Overexpression of cytoplasmic ZCCHC9 using transfection of ZCCHC9 cDNA in A549 and NCI-H1299 cells significantly upregulated the proliferation and invasion of these cancer cells in vitro (P < 0.05). Western blot study showed that overexpression of cytoplasmic ZCCHC9 significantly upregulated expression of p-JNK, Cyclin D1, and MMP7 (P < 0.05). Next we used the inhibitor of JNK pathway to inhibit the activity of the JNK pathway and the results showed that co-addition of SP600125 significantly abolished the function of ZCCHC9 to promote the proliferation and invasion of cancer cells. These results indicate that cytoplasmic ZCCHC9 could promote the proliferation and invasion of NSCLC through the JNK pathway and may be a promising cancer maker. 相似文献
973.
Jia Fan Wenyong Fan Jianzhen Lei Yingying Zhou Hongfei Xu Isha Kapoor Guoqing Zhu Juejin Wang 《生物化学与生物物理学报:疾病的分子基础》2019,1865(1):218-229
Pressure overload-induced cardiac hypertrophy occurs in response to chronic blood pressure increase, and dysfunction of CaV1.2 calcium channel involves in cardiac hypertrophic processes by perturbing intracellular calcium concentration ([Ca2+]i) and calcium-dependent signaling. As a carbohydrate-binding protein, galectin-1 (Gal-1) is found to bind with CaV1.2 channel, which regulates vascular CaV1.2 channel functions and blood pressure. However, the potential roles of Gal-1 in cardiac CaV1.2 channel (CaV1.2CM) and cardiomyocyte hypertrophy remain elusive. By whole-cell patch clamp, we find Gal-1 decreases the ICa,L with or without isoproterenol (ISO) application by reducing the channel membrane expression in neonatal rat ventricular myocytes (NRVMs). Moreover, Gal-1 could inhibit the current densities of CaV1.2CM by an alternative exon 9*-dependent manner in heterologously expressed HEK293 cells. Of significance, overexpression of Gal-1 diminishes ISO or KCl-induced [Ca2+]i elevation and attenuates ISO-induced hypertrophy in NRVMs. Mechanistically, Gal-1 decreases the ISO or Bay K8644-induced phosphorylation of intracellular calcium-dependent signaling proteins δCaMKII and HDAC4, and inhibits ISO-triggered translocation of HDAC4 in NRVMs. Pathologically, we observe that the expressions of Gal-1 and CaV1.2E9* channels are synchronously increased in rat hypertrophic cardiomyocytes and hearts. Taken together, our study indicates that Gal-1 reduces the channel membrane expression to inhibit the currents of CaV1.2CM in a splice-variant specific manner, which diminishes [Ca2+]i elevation, and attenuates cardiomyocyte hypertrophy by inhibiting the phosphorylation of δCaMKII and HDAC4. Furthermore, our work suggests that dysregulated Gal-1 and CaV1.2 alternative exon 9* might be attributed to the pathological processes of cardiac hypertrophy, and provides a potential anti-hypertrophic target in the heart. 相似文献
974.
975.
Translocator protein (TSPO) is a high-affinity cholesterol- and drug-binding mitochondrial protein. Nuclear receptor subfamily 5 group A member 1 or steroidogenic factor 1 (Nr5a1)-Cre mice were previously used to generate steroidogenic cell-specific Tspo gene conditional knockout (cKO) mice. TSPO-depleted homozygotes showed no response to adrenocorticotropic hormone (ACTH) in stimulating adrenal cortex corticosterone production but showed increased epinephrine synthesis in the medulla. No other phenotype was observed under normal growth conditions. During these studies, we noted that pairing two cKO mice resulted in the generation of small pups. These pups showed low growth rate at weaning, which has been linked to the development of type 2 diabetes (T2D) in adulthood. Experimental verification of T2D symptoms via blood testing of the adult mice, including glycated hemoglobin and insulin C-peptide measurements, showed that these Tspo cKO mice exhibited sustained hyperglycemia, a sign of prediabetes, likely due to the augmentation of hepatic glucose production mediated by the increased epinephrine. We also observed increased expression of the S100a8 gene, which is upregulated after chronic glucose stimulation. Taken together, the observed prediabetes phenotype and lack of response to ACTH indicate that Tspo cKO mice (Nr5a1-Cre+/?, Tspofl/fl) could provide a useful model to study the link between diabetes and stress. 相似文献
976.
Yiying Zeng Gadi V. P. Reddy Zhihong Li Yujia Qin Yannan Wang Xubin Pan Fan Jiang Feng Gao Zi‐Hua Zhao 《Journal of Applied Entomology》2019,143(3):165-176
Since the start of the 20th century, many invasive alien species (IAS) have spread rapidly around the world, causing serious threats to economies, societies and the environment. Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) is an important quarantine insect species in many countries that spread around the world over the last century. This review collected information on the distribution of B. dorsalis to explore the patterns of its invasion expansion. We found B. dorsalis to be distributed in 75 countries (comprised of 124 geographical distribution regions: provinces or states) in Asia, Africa, North America, South America and Oceania up to 2017. Asia and Africa were the most represented regions, accounting for 86.3% of the total number of countries. From 1910 to 1990, B. dorsalis was only found in five countries, but in the last three decades, it has experienced a sharp increase in its rate of spread, invading 70 more countries. Global temperature anomaly has significantly positive correlation with the spread of B. dorsalis. The results of this review provide a theoretical basis for understanding and predicting the continued spread of B. dorsalis under global changes. 相似文献
977.
Rama Natarajan Wei Bai Vaijayanthy Rangarajan Noe Gonzales Jia-li Gu Linda Lanting Jerry L. Nadler 《Journal of cellular physiology》1996,169(2):391-400
Platelet-derived growth factor BB (PDGF) is a potent mitogen and chemoattractant for vascular smooth muscle cells (VSMC). In the present study, we have examined the effects of PDGF on the 12-lipoxygenase (12-LO) pathway of arachidonate metabolism in porcine aortic VSMC (PVSMC). The rationale for this is previous studies showing that LO products have growth and chemotactic effects in VSMC and that another VSMC growth factor, angiotensin II, is a potent positive regulator of 12-LO activity and expression. We observed that PDGF causes a significant increase in the formation of the 12-LO product, 12-hydroxyeicosatetraenoic acid (12-HETE) in PVSMC. In addition, PDGF also markedly increased leukocyte-type 12-LO messenger RNA and protein expression. PDGF-induced PVSMC migration was inhibited significantly by two LO blockers but not by a cyclooxygenase blocker. Furthermore, although the proliferative effects of PDGF on PVSMC were not altered by cell culture under hyperglycemic conditions (25 mM glucose, HG), the chemotactic effects of PDGF as well as those of 10% fetal calf serum were significantly greater in cells cultured in HG as compared to normal glucose conditions (5.5 mM), thus indicating a potential new mechanism for the accelerated cardiovascular disease usually observed in diabetes. These results indicate a novel mechanism for the biological effects of PDGF in leading to cardiovascular disease. © 1996 Wiley-Liss, Inc. 相似文献
978.
979.
980.
云南省小黑山自然保护区种子植物区系研究 总被引:6,自引:1,他引:5
小黑山自然保护区有野生种子植物170科787属2195种。分析表明该区种子植物区系的地理成分复杂,联系广泛。热带性质的属有506属,占总属数的68.6%,温带性质的属有224属,占总属数的30.4%。热带性质的种890种,占总种数的40.9%,温带性质的种有1267种,占总种数的58.3%。表明该地区植物区系具有明显的亚热带性质,同时深受热带植物区系的影响。植物区系来源主要由东亚成分、热带亚洲成分(印度—马来西亚成分)、中国特有成分三部分融合而成。特有现象明显,有东亚特有科5科,中国特有属6属,中国特有种778种,占种总数的35.8%,而云南特有种有355种,占中国特有种的45.6%。保护区还拥有众多的珍稀濒危植物。 相似文献