全文获取类型
收费全文 | 33182篇 |
免费 | 731篇 |
国内免费 | 111篇 |
专业分类
系统科学 | 1180篇 |
丛书文集 | 451篇 |
教育与普及 | 36篇 |
理论与方法论 | 379篇 |
现状及发展 | 13172篇 |
研究方法 | 1265篇 |
综合类 | 17068篇 |
自然研究 | 473篇 |
出版年
2018年 | 767篇 |
2017年 | 791篇 |
2016年 | 536篇 |
2012年 | 678篇 |
2011年 | 1837篇 |
2010年 | 983篇 |
2009年 | 573篇 |
2008年 | 996篇 |
2007年 | 1500篇 |
2006年 | 538篇 |
2005年 | 612篇 |
2004年 | 737篇 |
2003年 | 713篇 |
2002年 | 635篇 |
2001年 | 860篇 |
2000年 | 829篇 |
1999年 | 587篇 |
1992年 | 556篇 |
1991年 | 388篇 |
1990年 | 420篇 |
1989年 | 406篇 |
1988年 | 403篇 |
1987年 | 413篇 |
1986年 | 454篇 |
1985年 | 580篇 |
1984年 | 403篇 |
1983年 | 333篇 |
1982年 | 294篇 |
1981年 | 319篇 |
1980年 | 370篇 |
1979年 | 869篇 |
1978年 | 678篇 |
1977年 | 652篇 |
1976年 | 521篇 |
1975年 | 513篇 |
1974年 | 770篇 |
1973年 | 640篇 |
1972年 | 704篇 |
1971年 | 763篇 |
1970年 | 1071篇 |
1969年 | 840篇 |
1968年 | 723篇 |
1967年 | 748篇 |
1966年 | 710篇 |
1965年 | 529篇 |
1959年 | 267篇 |
1958年 | 525篇 |
1957年 | 361篇 |
1956年 | 279篇 |
1954年 | 297篇 |
排序方式: 共有10000条查询结果,搜索用时 46 毫秒
991.
Vikas Rai Bhatnagar 《Systemic Practice and Action Research》2017,30(4):339-376
This insider action research study differentiates between developing leaders and leadership, evolves a systemic leadership model, and intervenes on the human, social and processes dimensions for developing leadership. This is a real-time study and responds to the organizational reality of fast pace of change and its systemic nature. Consequently, the research too is fast to guide actions and influence positive changes in the organization. As the action research addresses a systemic reality, research and contributions are in multiple aspects, with new techniques having huge implications for theory building as well as improving practice. The study provides a structural solution to perceived lack of commitment in senior colleagues—a syndrome I acronym as HILE (High Intentions and Lukewarm Execution)–by re-designing organizational processes and making time available for its effective utilization in developing leadership. A new technique of triggering major changes in organizations termed “concept sublimation” distils concept from the statements of major stakeholder and sublimates it from lower to higher unit of analysis and to higher levels of positivity. Statistical simplification of a competency framework by applying concepts from Euclidian geometry and making it effective is yet a unique contribution of this action research study. The study adapts the competing values framework in developing a method of assessing cultural congruence of a candidate with the culture of the organization. The uniqueness of the study lies in bridging the gap in the literature by actually and systemically developing leadership in an organization and providing pragmatic insights on developing leadership while also creating knowledge for theory building. 相似文献
992.
Learning organisation literature has widely discussed the connections between “double-loop” learning and its significance to organisational performance, but paying little attention to tools and systems that can operationalise “double-loop” learning in organisations. This paper investigates the impact of applying a systems approach for service operations design, expressed as the Vanguard Method (Seddon, Freedom from command and control: a better way to make the work work, 2003), in order to activate “double-loop” learning in service organisations. Two case studies were conducted in the banking mortgage operations and adults’ social care services in the UK, using the dimensions of the learning organisation questionnaire (DLOQ), semi-structured interviews, observations, and documents. The findings of the cross-case analysis support the link of applying the Vanguard Method with operationalising “double-loop” learning through three main factors, namely systematic-operations improvement, organisational capacity development, and outside-in mode of work; that are all embedded into the seven dimensions of the DLOQ. The value of this paper is the introduction of a service operations design tool that can activate “double-loop” learning performance in the fast changing knowledge era. It also provides an impetus for service organisations to creatively influence employees’ competencies to effectively improve internal systems. 相似文献
993.
V. Sala S. Bergerone S. Gatti S. Gallo A. Ponzetto C. Ponzetto T. Crepaldi 《Cellular and molecular life sciences : CMLS》2014,71(8):1439-1452
MicroRNAs (miRNAs) are natural, single-stranded, small RNA molecules which subtly control gene expression. Several studies indicate that specific miRNAs can regulate heart function both in development and disease. Despite prevention programs and new therapeutic agents, cardiovascular disease remains the main cause of death in developed countries. The elevated number of heart failure episodes is mostly due to myocardial infarction (MI). An increasing number of studies have been carried out reporting changes in miRNAs gene expression and exploring their role in MI and heart failure. In this review, we furnish a critical analysis of where the frontier of knowledge has arrived in the fields of basic and translational research on miRNAs in cardiac ischemia. We first summarize the basal information on miRNA biology and regulation, especially concentrating on the feedback loops which control cardiac-enriched miRNAs. A focus on the role of miRNAs in the pathogenesis of myocardial ischemia and in the attenuation of injury is presented. Particular attention is given to cardiomyocyte death (apoptosis and necrosis), fibrosis, neovascularization, and heart failure. Then, we address the potential of miR-diagnosis (miRNAs as disease biomarkers) and miR-drugs (miRNAs as therapeutic targets) for cardiac ischemia and heart failure. Finally, we evaluate the use of miRNAs in the emerging field of regenerative medicine. 相似文献
994.
Xingjian Jin Ashraf M. Mohieldin Brian S. Muntean Jill A. Green Jagesh V. Shah Kirk Mykytyn Surya M. Nauli 《Cellular and molecular life sciences : CMLS》2014,71(11):2165-2178
Primary cilia with a diameter of ~200 nm have been implicated in development and disease. Calcium signaling within a primary cilium has never been directly visualized and has therefore remained a speculation. Fluid-shear stress and dopamine receptor type-5 (DR5) agonist are among the few stimuli that require cilia for intracellular calcium signal transduction. However, it is not known if these stimuli initiate calcium signaling within the cilium or if the calcium signal originates in the cytoplasm. Using an integrated single-cell imaging technique, we demonstrate for the first time that calcium signaling triggered by fluid-shear stress initiates in the primary cilium and can be distinguished from the subsequent cytosolic calcium response through the ryanodine receptor. Importantly, this flow-induced calcium signaling depends on the ciliary polycystin-2 calcium channel. While DR5-specific agonist induces calcium signaling mainly in the cilioplasm via ciliary CaV1.2, thrombin specifically induces cytosolic calcium signaling through the IP3 receptor. Furthermore, a non-specific calcium ionophore triggers both ciliary and cytosolic calcium responses. We suggest that cilia not only act as sensory organelles but also function as calcium signaling compartments. Cilium-dependent signaling can spread to the cytoplasm or be contained within the cilioplasm. Our study thus provides the first model to understand signaling within the cilioplasm of a living cell. 相似文献
995.
A. Venerando L. Cesaro O. Marin A. Donella-Deana L. A. Pinna 《Cellular and molecular life sciences : CMLS》2014,71(12):2193-2196
The motif “SYDE”, incorporating the protein kinase CK2 consensus sequence (S-x-x-E) has been found to be phosphorylated at both its serine and tyrosine residues in several proteins. Of special interest is the case of cystic fibrosis Transmembrane-conductance Regulator (CFTR), where this motif is close to the residue (F508), whose deletion is the by far commonest cause of cystic fibrosis. Intriguingly, however, CFTR S511 cannot be phosphorylated by CK2 to any appreciable extent. Using a number of peptide substrates encompassing the CFTR “SYDE” site we have recently shown that: (1) failure of CK2 to phosphorylate the S511YDE motif is due to the presence of Y512; (2) CK2 readily phosphorylates S511 if Y512 is replaced by a phospho-tyrosine; (3) the Src family protein tyrosine kinase Lyn phosphorylates Y512 in a manner that is enhanced by the deletion of F508. These data, in conjunction with the recent observation that by inhibiting CK2 the degradation of F508delCFTR is reduced, lead us to hypothesize that the hierarchical phosphorylation of the motif SYDE by the concerted action of protein tyrosine kinases and CK2 is one of the mechanisms that cooperate to the premature degradation of F508delCFTR. 相似文献
996.
Jonathan Cools-Lartigue Jonathan Spicer Sara Najmeh Lorenzo Ferri 《Cellular and molecular life sciences : CMLS》2014,71(21):4179-4194
Neutrophils are being increasingly recognized as an important element in tumor progression. They have been shown to exert important effects at nearly every stage of tumor progression with a number of studies demonstrating that their presence is critical to tumor development. Novel aspects of neutrophil biology have recently been elucidated and its contribution to tumorigenesis is only beginning to be appreciated. Neutrophil extracellular traps (NETs) are neutrophil-derived structures composed of DNA decorated with antimicrobial peptides. They have been shown to trap and kill microorganisms, playing a critical role in host defense. However, their contribution to tumor development and metastasis has recently been demonstrated in a number of studies highlighting NETs as a potentially important therapeutic target. Here, studies implicating NETs as facilitators of tumor progression and metastasis are reviewed. In addition, potential mechanisms by which NETs may exert these effects are explored. Finally, the ability to target NETs therapeutically in human neoplastic disease is highlighted. 相似文献
997.
E. Hubin N. A. J. van Nuland K. Broersen K. Pauwels 《Cellular and molecular life sciences : CMLS》2014,71(18):3507-3521
The aggregation and deposition of the amyloid-β peptide (Aβ) in the brain has been linked with neuronal death, which progresses in the diagnostic and pathological signs of Alzheimer’s disease (AD). The transition of an unstructured monomeric peptide into self-assembled and more structured aggregates is the crucial conversion from what appears to be a harmless polypeptide into a malignant form that causes synaptotoxicity and neuronal cell death. Despite efforts to identify the toxic form of Aβ, the development of effective treatments for AD is still limited by the highly transient and dynamic nature of interconverting forms of Aβ. The variability within the in vivo “pool” of different Aβ peptides is another complicating factor. Here we review the dynamical interplay between various components that influence the heterogeneous Aβ system, from intramolecular Aβ flexibility to intermolecular dynamics between various Aβ alloforms and external factors. The complex dynamics of Aβ contributes to the causative role of Aβ in the pathogenesis of AD. 相似文献
998.
999.
J. Rodriguez B. Vernus I. Chelh I. Cassar-Malek J. C. Gabillard A. Hadj Sassi I. Seiliez B. Picard A. Bonnieu 《Cellular and molecular life sciences : CMLS》2014,71(22):4361-4371
Myostatin, a member of the transforming growth factor-β superfamily, is a potent negative regulator of skeletal muscle growth and is conserved in many species, from rodents to humans. Myostatin inactivation can induce skeletal muscle hypertrophy, while its overexpression or systemic administration causes muscle atrophy. As it represents a potential target for stimulating muscle growth and/or preventing muscle wasting, myostatin regulation and functions in the control of muscle mass have been extensively studied. A wealth of data strongly suggests that alterations in skeletal muscle mass are associated with dysregulation in myostatin expression. Moreover, myostatin plays a central role in integrating/mediating anabolic and catabolic responses. Myostatin negatively regulates the activity of the Akt pathway, which promotes protein synthesis, and increases the activity of the ubiquitin–proteasome system to induce atrophy. Several new studies have brought new information on how myostatin may affect both ribosomal biogenesis and translation efficiency of specific mRNA subclasses. In addition, although myostatin has been identified as a modulator of the major catabolic pathways, including the ubiquitin–proteasome and the autophagy–lysosome systems, the underlying mechanisms are only partially understood. The goal of this review is to highlight outstanding questions about myostatin-mediated regulation of the anabolic and catabolic signaling pathways in skeletal muscle. Particular emphasis has been placed on (1) the cross-regulation between myostatin, the growth-promoting pathways and the proteolytic systems; (2) how myostatin inhibition leads to muscle hypertrophy; and (3) the regulation of translation by myostatin. 相似文献
1000.
History has been disparaged since the late 19th century for not conforming to norms of scientific explanation. Nonetheless, as a matter of fact a work of history upends the regnant philosophical conception of science in the second part of the 20th century. Yet despite its impact, Kuhn’s Structure has failed to motivate philosophers to ponder why works of history should be capable of exerting rational influence on an understanding of philosophy of science. But all this constitutes a great irony and a mystery. The mystery consists of the persistence of a complete lack of interest in efforts to theorize historical explanation. Fundamental questions regarding why an historical account could have any rational influence remain not merely unanswered, but unasked. The irony arises from the fact that analytic philosophy of history went into an eclipse where it remains until this day just around the time that the influence of Kuhn’s great work began to make itself felt. This paper highlights puzzles long ignored regarding the challenges a work of history managed to pose to the epistemic authority of science, and what this might imply generally for the place of philosophy of history vis-à-vis the problems of philosophy. 相似文献