全文获取类型
收费全文 | 9324篇 |
免费 | 722篇 |
国内免费 | 426篇 |
专业分类
10472篇 |
出版年
2024年 | 22篇 |
2023年 | 79篇 |
2022年 | 236篇 |
2021年 | 391篇 |
2020年 | 271篇 |
2019年 | 281篇 |
2018年 | 316篇 |
2017年 | 254篇 |
2016年 | 374篇 |
2015年 | 560篇 |
2014年 | 615篇 |
2013年 | 708篇 |
2012年 | 803篇 |
2011年 | 735篇 |
2010年 | 466篇 |
2009年 | 340篇 |
2008年 | 476篇 |
2007年 | 394篇 |
2006年 | 379篇 |
2005年 | 313篇 |
2004年 | 270篇 |
2003年 | 231篇 |
2002年 | 225篇 |
2001年 | 170篇 |
2000年 | 187篇 |
1999年 | 137篇 |
1998年 | 84篇 |
1997年 | 81篇 |
1996年 | 77篇 |
1995年 | 59篇 |
1994年 | 63篇 |
1993年 | 48篇 |
1992年 | 90篇 |
1991年 | 76篇 |
1990年 | 77篇 |
1989年 | 61篇 |
1988年 | 47篇 |
1987年 | 67篇 |
1986年 | 45篇 |
1985年 | 37篇 |
1984年 | 33篇 |
1983年 | 20篇 |
1982年 | 25篇 |
1980年 | 22篇 |
1979年 | 26篇 |
1978年 | 19篇 |
1977年 | 21篇 |
1975年 | 18篇 |
1973年 | 21篇 |
1972年 | 17篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
51.
Effect of hypertonic conditions on protein synthesis in cells productively infected with simian virus 40. 总被引:5,自引:5,他引:0 下载免费PDF全文
Hypertonic medium selectively suppressed the synthesis of most host cell polypeptides relative to the synthesis of simian virus 40 capsid polypeptides and a minority of cellular polypeptides, notably histones. Under optimal hypertonic conditions, the synthesis of the major capsid polypeptide (VP1) is enhanced about sevenfold relative to host polypeptide synthesis. Because of the small amounts of the other nonhistone capsid polypeptides (VP2) and VP3) present in cell lysates, it was difficult to quantitate the extent, if any, of their enhancement. The maintenance of the restricted pattern of protein synthesis caused by hypertonic medium was dependent on continual peptide chain initiations. The resistance of viral protein synthesis to hypertonic conditions provides a means of detecting relatively low levels of intracellular viral protein synthesis. Analysis of the specific activity of the acid-soluble [3H]lysine pool indicated that the rate of incorporation of [3H]lysine into protein was an overestimation of the actual rate of overall protein synthesis occurring in cells exposed to hypertonic as compared to isotonic conditions. Since it is likely that both cellular and viral protein synthesis draw lysine from a single pool, this change in pool specific activity does not affect the analysis of relative rates of protein synthesis at a given level of tonicity. 相似文献
52.
53.
We have previously demonstrated an impaired insulin response to intraperitoneal glucose and arginine by the transplantable NEDH rat insulinoma. The nature of this tumour B-cell defect has been further studied by investigating the response of insulinoma-bearing rats to intravenous and intragastric glucose. Intravenous glucose failed to stimulate plasma immunoreactive insulin (IRI) above high basal levels (14.5 +/- 1.1 micrograms/L). However, significant elevation of the plasma IRI concentration was observed following an intragastric glucose load (17.1 +/- 1.5 micrograms/L; P less than 0.02). In view of the different effects of oral and intravenous glucose on insulin secretion in the RIN, implicating an involvement of incretin factors from the gut, the response of the tumour to GIP was investigated. Plasma IRI concentrations rose significantly in these animals (20.6 +/- 2.5 micrograms/L at 5 min, P less than 0.02). We conclude that (a) the transplantable rat insulinoma is responsive to GIP, and (b) that whilst the tumour B-cell has lost its insulin responsiveness to hyperglycaemia produced by intraperitoneal or intravenous glucose, it retains its ability to respond to intragastric glucose. This could be due to incretin factors from the gut of which GIP is currently the strongest candidate. 相似文献
54.
Three catabolic enzymes, 5'-nucleotidase (5'NT), adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) and one anabolic enzyme, myokinase (MK) involved in adenine nucleotide (AN) metabolism were studied in myocardium from 4 to 105 day old rats. The specific enzyme activities (nmoles/min/mg protein) at day 4 were 35.3 for 5'NT, 28.4 for ADA, 43.3 for PNP, and 5 X 10(3) for MK. At day 7, 5'NT, activities rose to 450%; PNP and ADA 150%; and MK 120%; of the day 4 level. The activities of the three catabolic enzymes were elevated for one or two weeks then declined rapidly. By day 34, they were slightly above the adult values. MK activity displayed a different time course. It continued to increase slowly with age after the initial surge. Compared to the adult heart, the total activities of these catabolic enzymes in the one- to three-week-old heart were 30% to 220% higher. This transient elevation in AN catabolic enzyme activities may be related to active DNA synthesis and cell proliferation occurred in the rat myocardium during the same period. 相似文献
55.
精液源性病毒增强因子(Semen-derived enhancer of viral infection,SEVI)是前列腺酸性磷酸酶(Prostatic acidphosphatase,PAP)位于PAP248-286的多肽片段,可增强人免疫缺陷病毒(Human immunodeficiency virus,HIV)的感染性。SEVI促进HIV感染的作用机制包括:①富含阳离子氨基酸残基的SEVI能通过静电作用降低HIV病毒颗粒与靶细胞之间的静电排斥;②SEVI在人体液中呈无序状态,利于病毒与靶细胞膜相互作用;③SEVI直接捕获HIV颗粒,提高病毒在靶细胞表面沉降速度,促进病毒与靶细胞的吸附和融合。目前已发现能抑制SEVI活性的物质包括:绿茶来源的EGCG(没食子儿茶素没食子酸酯)、氨基喹啉类小分子化合物Surfen、ThT类似物BTA-EG6等,能通过阻断HIV与SEVI结合或阻止其淀粉样纤维的形成,降低SEVI的病毒感染增强作用。研究SEVI的生物学特性及作用机制对防治HIV感染具有较为重要的指导意义。 相似文献
56.
Besides mediating the viral entry process, the human immunodeficiency virus (HIV-1) envelope protein gp41 can bind to many host cell components and regulate cell functions. Using a yeast two-hybrid system, we screened a human bone marrow cDNA library and identified a novel gp41-binding protein, CD74 (the MHC class II-associated invariant chain). Here, we report possible biological effects mediated by interaction between gp41 and CD74. We found that HIV-1 gp41 could bind directly to host CD74 in HIV-1-infected cells, and the peptide 6358 derived from gp41 loop region (aa 597-611) could effectively block the gp41-CD74 interaction. As a result of this binding, recombinant soluble gp41 and gp41 peptide 6358 activated the CD74-mediated ERK/MAPK pathway and significantly enhanced HIV-1 infection in vitro. Conversely, the enhancing effect could be suppressed by the recombinant CD74 extracellular domain. These results reveal a novel mechanism underlying gp41 mediation of HIV-1 infection and replication. 相似文献
57.
Dongchao Xu Ajuan Liu Xuan Wang Ming Zhang Zunyi Zhang Zhou Tan Mengsheng Qiu 《Developmental neurobiology》2018,78(1):39-50
Accurate quantification of gene expression is fundamental for understanding the molecular, genetic and functional bases of tissue development and diseases. Quantitative real‐time PCR (qPCR) is now the most widely used method of quantifying gene expression due to its simplicity, specificity, sensitivity, and wide quantification range. The use of appropriate reference genes to ensure accurate normalization is crucial for the correct quantification of gene expression from the early development, maturation, aging to injury processes in the central nervous system (CNS). In this study, we have determined the expression profiles of 12 candidate housekeeping genes (ACTB, CYC1, HMBS, GAPDH, HPRT1, RPL13A, YWHAZ, PPIA, RPLP0, TFRC, GUS, and 18S rRNA) in developing mouse brain and spinal cord. Throughout development, there was a significant degree of fluctuations in their expression levels, indicating the importance and complexity of finding appropriate reference genes. Three software including BestKeeper, geNorm and NormFinder were used to evaluate the stability of potential reference genes. GUS was the most stable gene and GUS/YWHAZ were the most stable reference gene pair across different developmental stages in different CNS regions, whereas HPRT1 and GAPDH were the most variable genes and thus inappropriate to use as reference genes. Therefore, our results identified GUS and YWHAZ as the best combination of two reference genes for expression data normalization in CNS developmental studies. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 39–50, 2018 相似文献
58.
The aim of the present study is to investigate the expression of a novel estrogen receptor, G protein-coupled receptor 30 (GPR30) and its correlation with matrix metalloproteinases-9 (MMP-9) in epithelial ovarian cancer (EOC). Ovary tissues were obtained from 39 female patients, including 30 cases of EOC and 9 cases of benign ovarian tumor. Four normal ovary tissues were used as control. Immunohistochemical staining was used to detect the expressions of GPR30 and MMP-9. Chi square test, Fisher's exact test and Spearman's rank correlation analysis were used for statistical analysis. The results showed that GPR30 overexpression rate in EOC cases was significantly higher than those in benign ovarian tumor and normal ovary cases. Whereas MMP-9 overexpression rate in EOC cases was significantly higher than that in normal ovary cases, without any difference to that in benign ovarian tumor cases. To demonstrate the relationship between GPR30 and clinicopathological variables of EOC, we further analyzed the pathology type, FIGO stage and age of patients sampled in our study. The analysis showed there were significant differences of GPR30 overexpression rate among various pathology types and different FIGO stages (P<0.05), and no significant difference of both GPR30 and MMP-9 among three age groups (P>0.05). Moreover, GPR30 expression was positively correlated with MMP-9 (r(s)=1.000, P=0.002). These results suggest that GPR30 may be involved in the invasion and metastasis of EOC, being a potential index of EOC early diagnosis and malignancy grade prediction. 相似文献
59.
Detection of the synergetic effects between variants, such as single-nucleotide polymorphisms (SNPs), is crucial for understanding the genetic characters of complex diseases. Here, we proposed a two-step approach to detect differentially inherited SNP modules (synergetic SNP units) from a SNP network. First, SNP-SNP interactions are identified based on prior biological knowledge, such as their adjacency on the chromosome or degree of relatedness between the functional relationships of their genes. These interactions form SNP networks. Second, disease-risk SNP modules (or sub-networks) are prioritised by their differentially inherited properties in IBD (Identity by Descent) profiles of affected and unaffected sibpairs. The search process is driven by the disease information and follows the structure of a SNP network. Simulation studies have indicated that this approach achieves high accuracy and a low false-positive rate in the identification of known disease-susceptible SNPs. Applying this method to an alcoholism dataset, we found that flexible patterns of susceptible SNP combinations do play a role in complex diseases, and some known genes were detected through these risk SNP modules. One example is GRM7, a known alcoholism gene successfully detected by a SNP module comprised of two SNPs, but neither of the two SNPs was significantly associated with the disease in single-locus analysis. These identified genes are also enriched in some pathways associated with alcoholism, including the calcium signalling pathway, axon guidance and neuroactive ligand-receptor interaction. The integration of network biology and genetic analysis provides putative functional bridges between genetic variants and candidate genes or pathways, thereby providing new insight into the aetiology of complex diseases. 相似文献
60.
Melanocytes are potential immunocompetent cells: evidence from recognition of immunological characteristics of cultured human melanocytes 总被引:5,自引:0,他引:5