全文获取类型
收费全文 | 49500篇 |
免费 | 130篇 |
国内免费 | 172篇 |
专业分类
系统科学 | 249篇 |
丛书文集 | 1052篇 |
教育与普及 | 108篇 |
理论与方法论 | 271篇 |
现状及发展 | 22218篇 |
研究方法 | 1875篇 |
综合类 | 23271篇 |
自然研究 | 758篇 |
出版年
2013年 | 360篇 |
2012年 | 666篇 |
2011年 | 1423篇 |
2010年 | 302篇 |
2008年 | 843篇 |
2007年 | 934篇 |
2006年 | 917篇 |
2005年 | 941篇 |
2004年 | 969篇 |
2003年 | 871篇 |
2002年 | 905篇 |
2001年 | 1408篇 |
2000年 | 1311篇 |
1999年 | 917篇 |
1992年 | 878篇 |
1991年 | 691篇 |
1990年 | 721篇 |
1989年 | 733篇 |
1988年 | 712篇 |
1987年 | 730篇 |
1986年 | 760篇 |
1985年 | 945篇 |
1984年 | 742篇 |
1983年 | 605篇 |
1982年 | 531篇 |
1981年 | 563篇 |
1980年 | 689篇 |
1979年 | 1546篇 |
1978年 | 1303篇 |
1977年 | 1270篇 |
1976年 | 952篇 |
1975年 | 995篇 |
1974年 | 1469篇 |
1973年 | 1240篇 |
1972年 | 1283篇 |
1971年 | 1509篇 |
1970年 | 2033篇 |
1969年 | 1602篇 |
1968年 | 1437篇 |
1967年 | 1508篇 |
1966年 | 1338篇 |
1965年 | 995篇 |
1964年 | 291篇 |
1959年 | 559篇 |
1958年 | 938篇 |
1957年 | 715篇 |
1956年 | 571篇 |
1955年 | 519篇 |
1954年 | 591篇 |
1948年 | 346篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
931.
Two new studies report mutations in FAN1 and three other genome-stability genes that tie the DNA damage response to progressive kidney failure and the dysfunction of several other organs. These findings provide clues to the underlying causes of tissue decline and may add a series of genes to the growing list of genome maintenance factors that protect against premature aging. 相似文献
932.
Steinbusch LK Schwenk RW Ouwens DM Diamant M Glatz JF Luiken JJ 《Cellular and molecular life sciences : CMLS》2011,68(15):2525-2538
Cardiomyocytes use glucose as well as fatty acids for ATP production. These substrates are transported into the cell by glucose
transporter 4 (GLUT4) and the fatty acid transporter CD36. Besides being located at the sarcolemma, GLUT4 and CD36 are stored
in intracellular compartments. Raised plasma insulin concentrations and increased cardiac work will stimulate GLUT4 as well
as CD36 to translocate to the sarcolemma. As so far studied, signaling pathways that regulate GLUT4 translocation similarly
affect CD36 translocation. During the development of insulin resistance and type 2 diabetes, CD36 becomes permanently localized
at the sarcolemma, whereas GLUT4 internalizes. This juxtaposed positioning of GLUT4 and CD36 is important for aberrant substrate
uptake in the diabetic heart: chronically increased fatty acid uptake at the expense of glucose. To explain the differences
in subcellular localization of GLUT4 and CD36 in type 2 diabetes, recent research has focused on the role of proteins involved
in trafficking of cargo between subcellular compartments. Several of these proteins appear to be similarly involved in both
GLUT4 and CD36 translocation. Others, however, have different roles in either GLUT4 or CD36 translocation. These trafficking
components, which are differently involved in GLUT4 or CD36 translocation, may be considered novel targets for the development
of therapies to restore the imbalanced substrate utilization that occurs in obesity, insulin resistance and diabetic cardiomyopathy. 相似文献
933.
934.
935.
Thomae AW Baltin J Pich D Deutsch MJ Ravasz M Zeller K Gossen M Hammerschmidt W Schepers A 《Cellular and molecular life sciences : CMLS》2011,68(22):3741-3756
In eukaryotes, binding of the six-subunit origin recognition complex (ORC) to DNA provides an interactive platform for the
sequential assembly of pre-replicative complexes. This process licenses replication origins competent for the subsequent initiation
step. Here, we analyze the contribution of human Orc6, the smallest subunit of ORC, to DNA binding and pre-replicative complex
formation. We show that Orc6 not only interacts with Orc1–Orc5 but also with the initiation factor Cdc6. Biochemical and imaging
experiments reveal that this interaction is required for licensing DNA replication competent. Furthermore, we demonstrate
that Orc6 contributes to the interaction of ORC with the chaperone protein HMGA1a (high mobility group protein A1a). Binding
of human ORC to replication origins is not specified at the level of DNA sequence and the functional organization of origins
is poorly understood. We have identified HMGA1a as one factor that might direct ORC to AT-rich heterochromatic regions. The
systematic analysis of the interaction between ORC and HMGA1a revealed that Orc6 interacts with the acidic C-terminus of HMGA1a
and also with its AT-hooks. Both domains support autonomous replication if targeted to DNA templates. As such, Orc6 functions
at different stages of the replication initiation process. Orc6 can interact with ORC chaperone proteins such as HMGA1a to
facilitate chromatin binding of ORC and is also an essential factor for pre-RC formation. 相似文献
936.
Rai A Nöthe H Tzvetkov N Korenbaum E Manstein DJ 《Cellular and molecular life sciences : CMLS》2011,68(16):2751-2767
Dictyostelium discoideum cells produce five dynamin family proteins. Here, we show that dynamin B is the only member of this group of proteins that
is initially produced as a preprotein and requires processing by mitochondrial proteases for formation of the mature protein.
Our results show that dynamin B-depletion affects many aspects of cell motility, cell-cell and cell-surface adhesion, resistance
to osmotic shock, and fatty acid metabolism. The mature form of dynamin B mediates a wide range and unique combination of
functions. Dynamin B affects events at the plasma membrane, peroxisomes, the contractile vacuole system, components of the
actin-based cytoskeleton, and cell adhesion sites. The modulating effect of dynamin B on the activity of the contractile vacuole
system is unique for the Dictyostelium system. Other functions displayed by dynamin B are commonly associated with either classical dynamins or dynamin-related
proteins. 相似文献
937.
938.
939.
Windus LC Chehrehasa F Lineburg KE Claxton C Mackay-Sim A Key B St John JA 《Cellular and molecular life sciences : CMLS》2011,68(19):3233-3247
Axons of primary olfactory neurons are intimately associated with olfactory ensheathing cells (OECs) from the olfactory epithelium until the final targeting of axons within the olfactory bulb. However, little is understood about the nature and role of interactions between OECs and axons during development of the olfactory nerve pathway. We have used high resolution time-lapse microscopy to examine the growth and interactions of olfactory axons and OECs in vitro. Transgenic mice expressing fluorescent reporters in primary olfactory axons (OMP-ZsGreen) and ensheathing cells (S100ß-DsRed) enabled us to selectively analyse these cell types in explants of olfactory epithelium. We reveal here that rather than providing only a permissive substrate for axon growth, OECs play an active role in modulating the growth of pioneer olfactory axons. We show that the interactions between OECs and axons were dependent on lamellipodial waves on the shaft of OEC processes. The motility of OECs was mediated by GDNF, which stimulated cell migration and increased the apparent motility of the axons, whereas loss of OECs via laser ablation of the cells inhibited olfactory axon outgrowth. These results demonstrate that the migration of OECs strongly regulates the motility of axons and that stimulation of OEC motility enhances axon extension and growth cone activity. 相似文献
940.
Alemu EA Sjøttem E Outzen H Larsen KB Holm T Bjørkøy G Johansen T 《Cellular and molecular life sciences : CMLS》2011,68(11):1953-1968
The protein kinase C (PKC) family of serine/threonine kinases consists of ten different isoforms grouped into three subfamilies,
denoted classical, novel and atypical PKCs (aPKCs). The aPKCs, PKCι/λ and PKCζ serve important roles during development and
in processes subverted in cancer such as cell and tissue polarity, cell proliferation, differentiation and apoptosis. In an
effort to identify novel interaction partners for aPKCs, we performed a yeast two-hybrid screen with the regulatory domain
of PKCι/λ as bait and identified the Krüppel-like factors family protein TIEG1 as a putative interaction partner for PKCι/λ.
We confirmed the interaction of both aPKCs with TIEG1 in vitro and in cells, and found that both aPKCs phosphorylate the DNA-binding
domain of TIEG1 on two critical residues. Interestingly, the aPKC-mediated phosphorylation of TIEG1 affected its DNA-binding
activity, subnuclear localization and transactivation potential. 相似文献