全文获取类型
收费全文 | 5687篇 |
免费 | 599篇 |
国内免费 | 1篇 |
专业分类
系统科学 | 1076篇 |
理论与方法论 | 275篇 |
现状及发展 | 947篇 |
研究方法 | 50篇 |
综合类 | 3939篇 |
出版年
2018年 | 727篇 |
2017年 | 732篇 |
2016年 | 432篇 |
2015年 | 31篇 |
2014年 | 6篇 |
2013年 | 2篇 |
2012年 | 268篇 |
2011年 | 965篇 |
2010年 | 820篇 |
2009年 | 456篇 |
2008年 | 523篇 |
2007年 | 779篇 |
2006年 | 13篇 |
2005年 | 51篇 |
2004年 | 138篇 |
2003年 | 159篇 |
2002年 | 65篇 |
2001年 | 5篇 |
2000年 | 11篇 |
1999年 | 3篇 |
1998年 | 2篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1991年 | 9篇 |
1990年 | 5篇 |
1989年 | 4篇 |
1988年 | 8篇 |
1987年 | 6篇 |
1986年 | 5篇 |
1984年 | 2篇 |
1983年 | 5篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1979年 | 5篇 |
1978年 | 4篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1974年 | 3篇 |
1973年 | 1篇 |
1971年 | 3篇 |
1970年 | 3篇 |
1969年 | 1篇 |
1968年 | 7篇 |
1967年 | 3篇 |
1966年 | 2篇 |
1965年 | 1篇 |
1964年 | 2篇 |
1957年 | 1篇 |
排序方式: 共有6287条查询结果,搜索用时 0 毫秒
231.
Macpherson AJ Martinic MM Harris N 《Cellular and molecular life sciences : CMLS》2002,59(12):2088-2096
There is an immense load of non-pathogenic commensal bacteria in the distal small intestine and the colon of mammals. The
physical barrier that prevents penetration (translocation) of these organisms into the body is a simple epithelium comprised
of the single enterocyte/colonocyte cell layer with its overlying mucus. In this review, we discuss the roles of intestinal
T cells in initiating and regulating innate and adaptive mucosal immune responses of the mucosal immune system that avoid
or limit penetration of the commensal intestinal bacteria.
Received 9 August 2002; accepted 9 September 2002
RID="*"
ID="*"Corresponding author. 相似文献
232.
233.
This study evaluates performance of information criteria used to separate latent classes. In the evaluations, various numbers
of latent classes, sample sizes, parameter structures and latent-class complexities were designed to simulate datasets. The
average accuracy rates of information criteria in selecting the designed numbers of latent classes were the core results in
this experiment. The study revealed that widely used information criteria, e.g., AIC, BIC, CAIC, could perform poorly under
some circumstances. By including a sample size adjustment (Rissanen, 1978), the unsatis-factory performances could be improved
considerably. The sample size adjustment provides a plausible solution for separating latent classes. Guidelines are provided
to help achieve optimum use of the model fit indices. 相似文献
234.
RUAN Ying DAI FuPing WEI BingBo 《科学通报(英文版)》2007,52(19):2630-2635
Rapid growth behavior of ζ phase has been investigated in the undercooling experiments of Cu-14%Ge, Cu-15%Ge, Cu-18.5%Ge and Cu-22%Ge alloys. Alloys of the four compositions obtain the maximum undercoolings of 202 K(0.17TL), 245 K(0.20TL), 223 K(0.20TL) and 176 K(0.17TL), respectively. As the content of Ge increases, the microstructural transition of "a(Cu) dendrite + ζ" peritectic phase → ζ" peritectic phase →, ζ dendrite + (ε+ζ) eutectic" takes place in the alloy at small undercooling, while the microstructural transition of "fragmented α (Cu)dendrite + ζ peritectic phase →, ζ peritectic phase →ζ dendrite + ε phase" happens in the alloy at large undercooling. EDS analysis of the Ge content in peritectic phase indicates that undercooling enlarges the solid solubility of ζ rdendrite, which leads to a decrease in the Ge content in ζ phase as undercooling increases. In the Cu-18.5%Ge alloy composed of ζ peritectic phase, the Ge content in ζ phase increases when undercooling increases, which is due to the restraint of the Ge enrichment on the grain boundaries by high undercooling effect. 相似文献
235.
236.
Takayuki Fujita Masanari Umemura Utako Yokoyama Satoshi Okumura Yoshihiro Ishikawa 《Cellular and molecular life sciences : CMLS》2017,74(4):591-606
As one of the most important second messengers, 3′,5′-cyclic adenosine monophosphate (cAMP) mediates various extracellular signals including hormones and neurotransmitters, and induces appropriate responses in diverse types of cells. Since cAMP was formerly believed to transmit signals through only two direct target molecules, protein kinase A and the cyclic nucleotide-gated channel, the sensational discovery in 1998 of another novel direct effecter of cAMP [exchange proteins directly activated by cAMP (Epac)] attracted a great deal of scientific interest in cAMP signaling. Numerous studies on Epac have since disclosed its important functions in various tissues in the body. Recently, observations of genetically manipulated mice in various pathogenic models have begun to reveal the in vivo significance of previous in vitro or cellular-level findings. Here, we focused on the function of Epac in the heart. Accumulating evidence has revealed that both Epac1 and Epac2 play important roles in the structure and function of the heart under physiological and pathological conditions. Accordingly, developing the ability to regulate cAMP-mediated signaling through Epac may lead to remarkable new therapies for the treatment of cardiac diseases. 相似文献
237.
238.
Maria C. Shina Annette Müller-Taubenberger Can Ünal Michael Schleicher Michael Steinert Ludwig Eichinger Rolf Müller Rosemarie Blau-Wasser Gernot Glöckner Angelika A. Noegel 《Cellular and molecular life sciences : CMLS》2011,68(2):303-313
Dictyostelium discoideum harbors a short (CRN12) and a long coronin (CRN7) composed of one and two beta-propellers, respectively. They are primarily
present in the cell cortex and cells lacking CRN12 (corA
−) or CRN7 (corB
−) have defects in actin driven processes. We compared the characteristics of a mutant cell line (corA
−
/corB
−) lacking CRN12 and CRN7 with the single mutants focusing on cytokinesis, phagocytosis, chemotaxis and development. Cytokinesis,
uptake of small particles, and developmental defects were not enhanced in the corA
−
/corB
− strain as compared to the single mutants, whereas motility and phagocytosis of yeast particles were more severely impaired.
It appears that although both proteins affect the same processes they do not act in a redundant manner. Rather, they often
act antagonistically, which is in accordance with their proposed roles in the actin cytoskeleton where CRN12 acts in actin
disassembly whereas CRN7 stabilizes actin filaments and protects them from disassembly. 相似文献
239.
Margherita Ratti Andrea Lampis Jens C. Hahne Rodolfo Passalacqua Nicola Valeri 《Cellular and molecular life sciences : CMLS》2018,75(22):4151-4162
Gastric cancer is one of the most aggressive malignancies, with limited treatment options in both locally advanced and metastatic setting, resulting in poor prognosis. Based on genomic characterization, stomach tumour has recently been described as a heterogeneous disease composed by different subtypes, each of them with peculiar molecular aspects and specific clinical behaviour. With an incidence of 22% among all western gastric tumour cases, stomach cancer with microsatellite instability was identified as one of these subgroups. Retrospective studies and limited prospective trials reported differences between gastric cancers with microsatellite stability and those with instability, mainly concerning clinical and pathological features, but also in regard to immunological microenvironment, correlation with prognostic value, and responses to treatment. In particular, gastric cancer with microsatellite instability constitutes a small but relevant subgroup associated with older age, female sex, distal stomach location, and lower number of lymph-node metastases. Emerging data attribute to microsatellite instability status a favourable prognostic meaning, whereas the poor outcomes reported after perioperative chemotherapy administration suggest a detrimental role of cytotoxic drugs in this gastric cancer subgroup. The strong immunogenicity and the widespread expression of immune-checkpoint ligands make microsatellite instability subtype more vulnerable to immunotherapeutic approach, e.g., with anti-PD-L1 and anti-CTLA4 antibodies. Since gastric cancer with microsatellite instability shows specific features and clinical behaviour not overlapping with microsatellite stable disease, microsatellite instability test might be suitable for inclusion in a diagnostic setting for all tumour stages to guarantee the most targeted and effective treatment to every patient. 相似文献
240.
Irina Kerkis Alvaro Rossan de Brandão Prieto da Silva Celine Pompeia Jan Tytgat Paulo L. de Sá Junior 《Cellular and molecular life sciences : CMLS》2017,74(4):647-661
Toxins have been shown to have many biological functions and to constitute a rich source of drugs and biotechnological tools. We focus on toxins that not only have a specific activity, but also contain residues responsible for transmembrane penetration, which can be considered bioportides—a class of cell-penetrating peptides that are also intrinsically bioactive. Bioportides are potential tools in pharmacology and biotechnology as they help deliver substances and nanoparticles to intracellular targets. Bioportides characterized so far are peptides derived from human proteins, such as cytochrome c (CYCS), calcitonin receptor (camptide), and endothelial nitric oxide synthase (nosangiotide). However, toxins are usually disregarded as potential bioportides. In this review, we discuss the inclusion of some toxins and molecules derived thereof as a new class of bioportides based on structure activity relationship, minimization, and biological activity studies. The comparative analysis of the amino acid residue composition of toxin-derived bioportides and their short molecular variants is an innovative analytical strategy which allows us to understand natural toxin multifunctionality in vivo and plan novel pharmacological and biotechnological products. Furthermore, we discuss how many bioportide toxins have a rigid structure with amphiphilic properties important for both cell penetration and bioactivity. 相似文献