全文获取类型
收费全文 | 1796篇 |
免费 | 2篇 |
国内免费 | 13篇 |
专业分类
系统科学 | 76篇 |
丛书文集 | 4篇 |
教育与普及 | 7篇 |
理论与方法论 | 26篇 |
现状及发展 | 214篇 |
研究方法 | 284篇 |
综合类 | 1042篇 |
自然研究 | 158篇 |
出版年
2021年 | 7篇 |
2020年 | 13篇 |
2019年 | 8篇 |
2018年 | 9篇 |
2017年 | 9篇 |
2016年 | 14篇 |
2015年 | 11篇 |
2014年 | 18篇 |
2013年 | 42篇 |
2012年 | 117篇 |
2011年 | 313篇 |
2010年 | 46篇 |
2009年 | 20篇 |
2008年 | 134篇 |
2007年 | 169篇 |
2006年 | 141篇 |
2005年 | 121篇 |
2004年 | 127篇 |
2003年 | 141篇 |
2002年 | 160篇 |
2001年 | 12篇 |
2000年 | 14篇 |
1999年 | 9篇 |
1998年 | 8篇 |
1997年 | 6篇 |
1996年 | 5篇 |
1995年 | 5篇 |
1994年 | 5篇 |
1993年 | 9篇 |
1992年 | 10篇 |
1991年 | 6篇 |
1990年 | 15篇 |
1989年 | 8篇 |
1988年 | 3篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 4篇 |
1983年 | 5篇 |
1982年 | 5篇 |
1980年 | 2篇 |
1979年 | 6篇 |
1978年 | 6篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1975年 | 7篇 |
1974年 | 4篇 |
1973年 | 8篇 |
1971年 | 7篇 |
1970年 | 2篇 |
1956年 | 1篇 |
排序方式: 共有1811条查询结果,搜索用时 31 毫秒
1.
从“十四五”保护与发展的生态关系角度,探讨了生态保护与绿色发展的十大生态关系,阐述了生态保护和绿色发展中的一系列有关生态关系的生态智慧及生态技术,并对长江、黄河等流域的生态保护和修复提出了相关建议。 相似文献
2.
ABSTRACTVideofilms of a foraging flying gurnard (Dactylopterus volitans) were collected at Itaipu, Niterói, RJ, Brazil. Analysis revealed details of the use of anterior parts of the pectoral fins which act as digging ‘hands’ to access infaunal prey items that are subsequently captured by oral suction feeding. Each pectoral fin has two distinct sections articulated separately on the pectoral girdle. The digging ‘anterior pectoral fin’ mainly consists of segmented and flexible fin rays but has an anterior robust unsegmented ray that provides an edge to the ‘hand’, allowing penetration of the substratum. The huge ‘posterior pectoral fins’ are supported by unsegmented rays. Most digging episodes involved one ‘hand’ and consisted of 1–7 cycles of movement with frequencies 1.15–3.74 cycles s?1. During a cycle, the ‘hand’ is moved forwards and medially above the substratum, then is twisted medially and simultaneously depressed so that the anterior unsegmented ray impacts and enters the substratum. The hand is then drawn backwards and laterally to disturb the substratum. To prevent upward pitching of the head during digging, the ‘posterior pectoral fins’ are both moved anteriorly and laterally to shift the centre of gravity forwards while the caudal and ?second dorsal fins continue to provide propulsive force. 相似文献
3.
Fibulin-5/DANCE is essential for elastogenesis in vivo. 总被引:19,自引:0,他引:19
Tomoyuki Nakamura Pilar Ruiz Lozano Yasuhiro Ikeda Yoshitaka Iwanaga Aleksander Hinek Susumu Minamisawa Ching-Feng Cheng Kazuhiro Kobuke Nancy Dalton Yoshikazu Takada Kei Tashiro John Ross Jr Tasuku Honjo Kenneth R Chien 《Nature》2002,415(6868):171-175
The elastic fibre system has a principal role in the structure and function of various types of organs that require elasticity, such as large arteries, lung and skin. Although elastic fibres are known to be composed of microfibril proteins (for example, fibrillins and latent transforming growth factor (TGF)-beta-binding proteins) and polymerized elastin, the mechanism of their assembly and development is not well understood. Here we report that fibulin-5 (also known as DANCE), a recently discovered integrin ligand, is an essential determinant of elastic fibre organization. fibulin-5-/- mice generated by gene targeting exhibit a severely disorganized elastic fibre system throughout the body. fibulin-5-/- mice survive to adulthood, but have a tortuous aorta with loss of compliance, severe emphysema, and loose skin (cutis laxa). These tissues contain fragmented elastin without an increase of elastase activity, indicating defective development of elastic fibres. Fibulin-5 interacts directly with elastic fibres in vitro, and serves as a ligand for cell surface integrins alphavbeta3, alphavbeta5 and alpha9beta1 through its amino-terminal domain. Thus, fibulin-5 may provide anchorage of elastic fibres to cells, thereby acting to stabilize and organize elastic fibres in the skin, lung and vasculature. 相似文献
4.
John C. Oliga 《Systemic Practice and Action Research》1988,1(1):87-112
In social systems science generally, and in management science particularly, recent developments in the variety of types of specific problem-solving methodologies (under the rubric of hard and soft systems approaches) have given an impetus to a line of inquiry, as well as debate on the nature of those methodologies. On the one hand, there has been the view that what we are witnessing is a form of Kuhnian crisis. On the other hand, a complementarist view of developments has been argued and a contingency approach proposed. But one thing has been common among the competing views: a belief that the prospects for further advances in the design and application of those methodologies, and in resolving the current controversies, lie in serious attempts to reconsider and clarify the underlying metatheoretical assumptions and concerns. This paper is an attempt to contribute to such an endeavor. A brief exposition of three methodological foundations (namely, empiricism, hermeneutics, and critique) is made, not only with the purpose of highlighting the nature as well as the limits of their epistemological and ethical claims, but also as a basis for illuminating both the nature of contemporary work on systems inquiry, design, and problem solving and the ongoing debate on what constitutes appropriate criteria for choice of specific methodologies. 相似文献
5.
6.
RNA-DNA hybrids at the cytological level 总被引:37,自引:0,他引:37
7.
John Zhang 《华南师范大学学报(自然科学版)》2014,46(6):134-134
正We describe a theoretical approach based on fragment method for quantum mechanical calculation of proteins.In this approach,complete quantum mechanical calculation of protein energies in solvent is carried out by fragment which is then feed into molecular dynamics simulation to study protein dynamics.This approach extends computational study of protein dynamics to the fully quantum mechanical level,beyond tradiationl force field methods.Pt 相似文献
8.
Purification and cloning of amyloid precursor protein beta-secretase from human brain 总被引:40,自引:0,他引:40
Sinha S Anderson JP Barbour R Basi GS Caccavello R Davis D Doan M Dovey HF Frigon N Hong J Jacobson-Croak K Jewett N Keim P Knops J Lieberburg I Power M Tan H Tatsuno G Tung J Schenk D Seubert P Suomensaari SM Wang S Walker D Zhao J McConlogue L John V 《Nature》1999,402(6761):537-540
Proteolytic processing of the amyloid precursor protein (APP) generates amyloid beta (Abeta) peptide, which is thought to be causal for the pathology and subsequent cognitive decline in Alzheimer's disease. Cleavage by beta-secretase at the amino terminus of the Abeta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated carboxy-terminal fragment. Cleavage of the C-terminal fragment by gamma-secretase(s) leads to the formation of Abeta. The pathogenic mutation K670M671-->N670L671 at the beta-secretase cleavage site in APP, which was discovered in a Swedish family with familial Alzheimer's disease, leads to increased beta-secretase cleavage of the mutant substrate. Here we describe a membrane-bound enzyme activity that cleaves full-length APP at the beta-secretase cleavage site, and find it to be the predominant beta-cleavage activity in human brain. We have purified this enzyme activity to homogeneity from human brain using a new substrate analogue inhibitor of the enzyme activity, and show that the purified enzyme has all the properties predicted for beta-secretase. Cloning and expression of the enzyme reveals that human brain beta-secretase is a new membrane-bound aspartic proteinase. 相似文献
9.
Mouquet H Scheid JF Zoller MJ Krogsgaard M Ott RG Shukair S Artyomov MN Pietzsch J Connors M Pereyra F Walker BD Ho DD Wilson PC Seaman MS Eisen HN Chakraborty AK Hope TJ Ravetch JV Wardemann H Nussenzweig MC 《Nature》2010,467(7315):591-595
During immune responses, antibodies are selected for their ability to bind to foreign antigens with high affinity, in part by their ability to undergo homotypic bivalent binding. However, this type of binding is not always possible. For example, the small number of gp140 glycoprotein spikes displayed on the surface of the human immunodeficiency virus (HIV) disfavours homotypic bivalent antibody binding. Here we show that during the human antibody response to HIV, somatic mutations that increase antibody affinity also increase breadth and neutralizing potency. Surprisingly, the responding naive and memory B cells produce polyreactive antibodies, which are capable of bivalent heteroligation between one high-affinity anti-HIV-gp140 combining site and a second low-affinity site on another molecular structure on HIV. Although cross-reactivity to self-antigens or polyreactivity is strongly selected against during B-cell development, it is a common serologic feature of certain infections in humans, including HIV, Epstein-Barr virus and hepatitis C virus. Seventy-five per cent of the 134 monoclonal anti-HIV-gp140 antibodies cloned from six patients with high titres of neutralizing antibodies are polyreactive. Despite the low affinity of the polyreactive combining site, heteroligation demonstrably increases the apparent affinity of polyreactive antibodies to HIV. 相似文献
10.
Ngo VN Davis RE Lamy L Yu X Zhao H Lenz G Lam LT Dave S Yang L Powell J Staudt LM 《Nature》2006,441(7089):106-110
The pursuit of novel therapeutic agents in cancer relies on the identification and validation of molecular targets. Hallmarks of cancer include self-sufficiency in growth signals and evasion from apoptosis; genes that regulate these processes may be optimal for therapeutic attack. Here we describe a loss-of-function screen for genes required for the proliferation and survival of cancer cells using an RNA interference library. We used a doxycycline-inducible retroviral vector for the expression of small hairpin RNAs (shRNAs) to construct a library targeting 2,500 human genes. We used retroviral pools from this library to infect cell lines representing two distinct molecular subgroups of diffuse large B-cell lymphoma (DLBCL), termed activated B-cell-like DLBCL and germinal centre B-cell-like DLBCL. Each vector was engineered to contain a unique 60-base-pair 'bar code', allowing the abundance of an individual shRNA vector within a population of transduced cells to be measured using microarrays of the bar-code sequences. We observed that a subset of shRNA vectors was depleted from the transduced cells after three weeks in culture only if shRNA expression was induced. In activated B-cell-like DLBCL cells, but not germinal centre B-cell-like DLBCL cells, shRNAs targeting the NF-kappaB pathway were depleted, in keeping with the essential role of this pathway in the survival of activated B-cell-like DLBCL. This screen uncovered CARD11 as a key upstream signalling component responsible for the constitutive IkappaB kinase activity in activated B-cell-like DLBCL. The methodology that we describe can be used to establish a functional taxonomy of cancer and help reveal new classes of therapeutic targets distinct from known oncogenes. 相似文献