全文获取类型
收费全文 | 2233篇 |
免费 | 219篇 |
国内免费 | 140篇 |
专业分类
2592篇 |
出版年
2024年 | 5篇 |
2023年 | 54篇 |
2022年 | 42篇 |
2021年 | 98篇 |
2020年 | 110篇 |
2019年 | 174篇 |
2018年 | 89篇 |
2017年 | 63篇 |
2016年 | 45篇 |
2015年 | 47篇 |
2014年 | 91篇 |
2013年 | 133篇 |
2012年 | 46篇 |
2011年 | 84篇 |
2010年 | 53篇 |
2009年 | 74篇 |
2008年 | 83篇 |
2007年 | 101篇 |
2006年 | 100篇 |
2005年 | 84篇 |
2004年 | 67篇 |
2003年 | 94篇 |
2002年 | 89篇 |
2001年 | 65篇 |
2000年 | 41篇 |
1999年 | 54篇 |
1998年 | 47篇 |
1997年 | 53篇 |
1996年 | 53篇 |
1995年 | 56篇 |
1994年 | 48篇 |
1993年 | 37篇 |
1992年 | 40篇 |
1991年 | 26篇 |
1990年 | 36篇 |
1989年 | 19篇 |
1988年 | 20篇 |
1987年 | 22篇 |
1986年 | 19篇 |
1985年 | 21篇 |
1984年 | 28篇 |
1983年 | 23篇 |
1982年 | 25篇 |
1981年 | 18篇 |
1980年 | 5篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1976年 | 4篇 |
1975年 | 1篇 |
排序方式: 共有2592条查询结果,搜索用时 15 毫秒
991.
The detection, surveillance and treatment of premalignant gastric lesions related to Helicobacter pylori infection 总被引:2,自引:0,他引:2
Gastric cancer is an important worldwide health problem and causes considerable morbidity and mortality. It represents the second leading cause of cancer-related death worldwide. A cascade of recognizable precursor lesions precedes most distal gastric carcinomas. In this multistep model of gastric carcinogenesis, Helicobacter pylori causes chronic active inflammation of the gastric mucosa, which slowly progresses through the premalignant stages of atrophic gastritis, intestinal metaplasia and dysplasia to gastric carcinoma. Detection and treatment of premalignant lesions may thus provide a basis for gastric cancer prevention. However, at present, premalignant changes of the gastric mucosa are frequently disregarded in clinical practice or result in widely varying follow-up frequency or treatment. This review provides an overview of current knowledge on detection, surveillance and treatment of patients with premalignant gastric lesions, and identifies the uncertainties that require further research. 相似文献
992.
Gruber A Lell CP Spruth M Lass-Flörl C Speth C Stoiber H Hube B Coleman D Polonelli L Dierich MP Würzner R 《FEMS immunology and medical microbiology》2003,37(1):77-83
Oral candidiasis in HIV-1-infected individuals is widely believed to be triggered by the acquired T-lymphocyte immunodeficiency. Recently, binding of the HIV-1 envelope protein gp160 and its subunit gp41, and also of the whole virus itself, to Candida albicans has been shown. The present study shows that, in addition to C. albicans, HIV-1 gp41 also binds to yeast and hyphal forms of Candida dubliniensis, a species which is closely related to C. albicans, and to Candida tropicalis but not to Candida krusei, Candida glabrata or Saccharomyces cerevisiae. The previous finding that gp41 binding to C. albicans augments fungal virulence in vitro is supported by the observation that the yeast showed an enhanced adhesion to HIV-infected H9 cells in comparison to uninfected cells. In line with these results soluble gp41 itself reduced binding of C. albicans to both endothelial and epithelial cell lines, confirming a dominant role of the gp41 binding moiety on the surface of Candida for adhesion. Surface-associated secreted aspartic proteinases (Saps) play an important role in candidial adhesion, but are not likely to be involved in the interaction as gp41 binding to the C. albicans parental wild-type strain was comparable to that of three different isogenic Sap deletion mutants. Furthermore, gp41 binding to the yeast killer toxin-susceptible C. albicans strain 10S was not inhibitable by an anti-YKT receptor antibody. In conclusion, HIV-1 interacts with different clinically important Candida spp., and may thereby affect the outcome of the respective fungal infection. 相似文献
993.
994.
Tongsen Zheng Xianzhi Meng JiaBei Wang Xi Chen Dalong Yin Yingjian Liang Xuan Song Shangha Pan Hongchi Jiang Lianxin Liu 《Journal of cellular biochemistry》2010,111(1):218-228
FTY720, a new immunosuppressant, derived from ISP‐1, has been studied for its putative anti‐cancer properties in the recent years. In this study, we have reported that FTY720 greatly inhibited gastric cancer cell proliferation for the first time, and found this effect was associated with G1 phase cell cycle arrest and apoptosis. Results from our Western blotting and Real‐time PCR showed that FTY720 induced obvious PTEN expression in a p53‐independent way, consistent with a substantial decrease in p‐Akt and MDM2. FTY720 dramatically increased the expression of Cip1/p21, p27, and BH3‐only proteins through the accumulation of p53 by PTEN‐mediated inhibition of the PI3K/Akt/MDM2 signaling. Suppression of PTEN expression with siRNA significantly reduced the p53 and p21 levels and activated Akt, resulting in decreased apoptosis and increased cell survival. Furthermore, we have observed an additive effect of FTY720 in killing gastric cancer cells when in combination with Cisplatin, partly through PTEN‐mediated Akt/MDM2 inhibition. In vivo study has also shown that tumor growth was significantly suppressed after FTY720 treatment. In conclusion, our results suggest that FTY720 induces a significant increase of PTEN, which inhibits p‐Akt and MDM2, and then increases the level of p53, thereby inducing G1 phase arrest and apoptosis. We have characterized a novel immunosuppressant, for the first time, which shows potential anti‐tumor effects on gastric cancer by PTEN activation through p53‐independent mechanism, especially in combination with Cisplatin. This PTEN target‐based therapy is worth further investigation and warrants clinical evaluation. J. Cell. Biochem. 111: 218–228, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
995.
E. V. Shakirov L. A. Gabdrakhmanova N. P. Balaban M. R. Sharipova G. N. Rudenskaya I. B. Leshchinskaya 《Microbiology》2000,69(1):21-25
The effect of nutrients and growth conditions on the accumulation of glutamyl endopeptidase in the culture liquid ofBacillus intermedius 3–19 was studied. Glucose and other readily metabolizable carbon sources were found to suppress the production of the enzyme,
whereas inorganic phosphate and ammonium cations enhanced it. Protein substrates, such as casein, gelatin, and hemoglobin,
did not affect enzyme production. Some bivalent cations (Ca2+, Mg2+, Co2+) increased the production of glutamyl endopeptidase, but others (Zn2+, Fe2+, Cu2+) acted in the opposite way. The rate of enzyme accumulation in the culture liquid increased as the growth rate of the bacterium
decreased, so that the maximum enzyme activity was observed in the stationary growth phase. Based on the results of this investigation,
an optimal medium for the maximum production of glutamyl endopeptidase byB. intermedius 3–19 was elaborated. 相似文献
996.
Fujimoto T Tomitaka Y Abe H Tsuda S Futai K Mizukubo T 《Journal of plant physiology》2011,168(10):1084-1097
We investigated what gene(s) in the plant roots have the positive role against repressing root-knot nematode (RKN) infection. We investigated the interaction between RKN infection and gene expression in the plant roots induced by methyl jasmonate (MeJA). We focused on the induced resistance response and the duration after foliar treatment with MeJA of 0.1, 0.5, 1.0, and 5.0mM at 1, 24, 48, and 72h prior to the inoculation of RKN. As a result, the foliar treatment with MeJA at 0.5mM or higher concentrations significantly reduced the infection of RKN in plants and the effect lasted for about 1 week. The repressing effect on RKN population declined to the lowest level in two weeks after MeJA treatment. The expression of proteinase inhibitors (PIs) and multicystatin (MC) were induced while the repressing effect on RKN was valid and a negative correlation was found between the expression of PIs or MC and RKN infection. In addition, when tomato plants no longer expressing MC and PIs were treated again with MeJA, the repressing effect revived. These phenomena appeared to be regardless of the existence of Mi-genes or isolate of RKN. Our results indicate that the expression level of MC and PIs may be effective as marker genes for estimating the induced resistance response against RKN infection. 相似文献
997.
Riedt CS Brolin RE Sherrell RM Field MP Shapses SA 《Obesity (Silver Spring, Md.)》2006,14(11):1940-1948
Objective: Roux‐en‐Y gastric bypass (RYGB) is considered to be the gold standard alternative treatment for severe obesity. Weight loss after RYGB results primarily from decreased food intake. Inadequate calcium (Ca) intake and metabolic bone disease can occur after gastric bypass. To our knowledge, whether malabsorption of Ca contributes to an altered Ca metabolism in the RYGB patient has not been addressed previously. Research Methods and Procedures: We recruited 25 extremely obese women in order to study true fractional Ca absorption (TFCA) before and 6 months after RYGB surgery, using a dual stable isotope method (42Ca and 43Ca) and test load of Ca (200 mg). Hormones regulating Ca absorption and markers of bone turnover were also measured. Results: In 21 women (BMI 52.7 ± 8.3 kg/m2, age 43.9 ± 10.4 years) who successfully completed the study, TFCA decreased from 0.36 ± 0.08 to 0.24 ± 0.09 (p < 0.001) after RYGB. Bone turnover markers increased significantly (p < 0.01). TFCA correlated with estradiol levels (r = 0.512, p < 0.02) and tended to correlate with 1,25 (OH)2D (r = 0.427, p < 0.06) at final measurement. Stepwise linear regression indicated that estradiol explained 62% of the variance for TFCA at 6 months post‐surgery (p < 0.01). Discussion: TFCA decreases (0.12 ± 0.08) after RYGB surgery but remains within normal range. Although only some patients were estimated to have low Ca absorption after surgery, all of the patients showed a dramatic increase in markers of bone resorption. The alteration in Ca metabolism after RYGB‐induced weight loss appears to be regulated primarily by estradiol levels and might ultimately affect bone mass. 相似文献
998.
We recently characterized the proteinase-activated receptor (PAR)-2, a G protein-coupled receptor (GPCR), as the first cargo protein recognized by p24A. Here, we demonstrate that p24A binds to several other GPCRs, including PAR-1, the nucleotide receptors P2Y(1), P2Y(2), P2Y(4), and P2Y(11), as well as the μ-opioid receptor 1B. The acidic amino acid residues Glu and Asp at the second extracellular loop of GPCRs are essential for interaction with p24A. p23, another member of the p24 family, also interacts with GPCRs, similar to p24A. However, p23 shows a delayed dissociation from PAR-2 after activation of PAR-2, compared to the dissociation between PAR-2 and p24A. p24A and p23 arrest both P2Y(4) receptor and μ-opioid receptor 1B at the intracellular compartments, as observed for PAR-2. A comparable result was obtained when we studied primary rat astrocytes in culture. Over-expression of the N-terminal p24A fragment impairs PAR-2 resensitization in astrocytes that extends our findings to a native system. In summary, we demonstrate that p24A and p23 are specific cargo receptors of GPCRs and differentially control GPCR trafficking in the biosynthetic pathway, and thereby, p24A and p23 regulate GPCR signaling in astrocytes. 相似文献
999.
拉曼光谱是一种分子振动光谱技术,具有分子水平的肿瘤检测和诊断能力.胃癌是常见恶性肿瘤,经常到晚期才得到诊断,死亡率较高,而早期胃癌预后较好,因此胃癌早期检测和诊断显得尤为重要.文章介绍了拉曼光谱用于胃癌早期检测和诊断的应用,并综述其研究进展,结果认为拉曼光谱探针与内镜整合,将实现胃癌活体检测和诊断,极具临床应用价值. 相似文献
1000.
Su-Zhen Song Sen Lin Jia-Ning Liu Ming-Bao Zhang Ya-Ting Du Dong-Dong Zhang Wei-Hua Xu Hong-Bo Wang 《Journal of cellular physiology》2019,234(10):18587-18601
Gastric cancer (GC) is a common heterogeneous disease. The critical roles of microRNA-340 (miR-340) in the development and progression of GC were emphasized in accumulating studies. This study aims to examine the regulatory mechanism of miR-340 in GC cellular processes. Initially, microarray technology was used to identify differentially expressed genes and regulatory miRs in GC. After that, the potential role of miR-340 in GC was determined via ectopic expression, depletion, and reporter assay experiments. Expression of secreted phosphoprotein 1 (SPP1), miR-340, phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway, and epithelial–mesenchymal transition (EMT)-related genes was measured. Moreover, to further explore the function of miR-340 in vivo and in vitro, proliferation, apoptosis, migration, invasion, and tumorigenic capacity were evaluated. SPP1 was a target gene of miR-340 which could then mediate the PI3K/AKT signaling pathway by targeting SPP1 in GC. Furthermore, miR-340 levels were reduced and SPP1 was enriched in GC tissues and cells, with the PI3K/AKT signaling pathway being activated. Inhibitory effects of upregulated miR-340 on SPP1 and the PI3K/AKT signaling pathway were confirmed in vivo and in vitro. Overexpression of miR-340 or the silencing of SPP1 inhibited GC cell proliferation, invasion, migration, and EMT process, but promoted apoptosis of GC cells. Typically, targeting of SPP1 by miR-340 may contribute to the inhibition of proliferation, migration, invasion, and EMT of GC cells via suppression of PI3K/AKT signaling pathway. 相似文献