全文获取类型
收费全文 | 34189篇 |
免费 | 90篇 |
国内免费 | 88篇 |
专业分类
系统科学 | 283篇 |
丛书文集 | 591篇 |
教育与普及 | 73篇 |
理论与方法论 | 110篇 |
现状及发展 | 13980篇 |
研究方法 | 1307篇 |
综合类 | 17376篇 |
自然研究 | 647篇 |
出版年
2013年 | 265篇 |
2012年 | 428篇 |
2011年 | 1091篇 |
2010年 | 185篇 |
2008年 | 516篇 |
2007年 | 616篇 |
2006年 | 628篇 |
2005年 | 614篇 |
2004年 | 595篇 |
2003年 | 589篇 |
2002年 | 523篇 |
2001年 | 1189篇 |
2000年 | 1130篇 |
1999年 | 635篇 |
1992年 | 638篇 |
1991年 | 549篇 |
1990年 | 574篇 |
1989年 | 530篇 |
1988年 | 540篇 |
1987年 | 526篇 |
1986年 | 536篇 |
1985年 | 680篇 |
1984年 | 537篇 |
1983年 | 473篇 |
1982年 | 389篇 |
1981年 | 392篇 |
1980年 | 488篇 |
1979年 | 1050篇 |
1978年 | 859篇 |
1977年 | 801篇 |
1976年 | 687篇 |
1975年 | 797篇 |
1974年 | 1029篇 |
1973年 | 864篇 |
1972年 | 896篇 |
1971年 | 1066篇 |
1970年 | 1370篇 |
1969年 | 1030篇 |
1968年 | 989篇 |
1967年 | 946篇 |
1966年 | 897篇 |
1965年 | 634篇 |
1964年 | 153篇 |
1959年 | 379篇 |
1958年 | 590篇 |
1957年 | 441篇 |
1956年 | 367篇 |
1955年 | 343篇 |
1954年 | 354篇 |
1948年 | 248篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
911.
Cohausz O Blenn C Malanga M Althaus FR 《Cellular and molecular life sciences : CMLS》2008,65(4):644-655
Poly(ADP-ribose) (PAR) has been identified as a DNA damage-inducible cell death signal upstream of apoptosis-inducing factor
(AIF). PAR causes the translocation of AIF from mitochondria to the nucleus and triggers cell death. In living cells, PAR
molecules are subject to dynamic changes pending on internal and external stress factors. Using RNA interference (RNAi), we
determined the roles of poly(ADP-ribose) polymerases-1 and -2 (PARP-1, PARP-2) and poly(ADP-ribose) glycohydrolase (PARG),
the key enzymes configuring PAR molecules, in cell death induced by an alkylating agent. We found that PARP-1, but not PARP-2
and PARG, contributed to alkylation-induced cell death. Likewise, AIF translocation was only affected by PARP-1. PARP-1 seems
to play a major role configuring PAR as a death signal involving AIF translocation regardless of the death pathway involved.
Received 7 November 2007; received after revision 19 December 2007; accepted 21 December 2007
O. Cohausz, C. Blenn: These two authors contributed equally to this work. 相似文献
912.
Dolezel D Zdechovanova L Sauman I Hodkova M 《Cellular and molecular life sciences : CMLS》2008,65(6):964-969
Current models state that insect peripheral oscillators are directly responsive to light, while mammalian peripheral clock
genes are coordinated by a master clock in the brain via intermediate factors, possibly hormonal. We show that the expression
levels of two circadian clock genes, period (per) and Par Domain Protein 1 (Pdp1) in the peripheral tissue of an insect model species, the linden bug Pyrrhocoris apterus, are inversely affected by contrasting photoperiods. The effect of photoperiod on per and Pdp1 mRNA levels was found to be mediated by the corpus allatum, an endocrine gland producing juvenile hormone. Our results
provide the first experimental evidence for the effect of an endocrine gland on circadian clock gene expression in insects.
Received 31 October 2007; received after revision 7 January 2008; accepted 9 January 2008
D. Dolezel, L. Zdechovanova: These authors contributed equally to this work. 相似文献
913.
Beside its role as a neurotransmitter in the central nervous system, serotonin appears to be a central physiologic mediator
of many gastrointestinal (GI) functions and a mediator of the brain-gut connection. By acting directly and via modulation
of the enteric nervous system, serotonin has numerous effects on the GI tract. The main gut disturbances in which serotonin
is involved are acute chemotherapy-induced nausea and vomiting, carcinoid syndrome and irritable bowel syndrome. Serotonin
also has mitogenic properties. Platelet-derived serotonin is involved in liver regeneration after partial hepatectomy. In
diseased liver, serotonin may play a crucial role in the progression of hepatic fibrosis and the pathogenesis of steatohepatitis.
Better understanding of the role of the serotonin receptor subtypes and serotonin mechanisms of action in the liver and gut
may open new therapeutic strategies in hepato-gastrointestinal diseases.
Received 15 August 2007; received after revision 1 November 2007; accepted 5 November 2007 相似文献
914.
Cajal bodies (CBs) and Gems are nuclear domains that contain factors responsible for spliceosomal small nuclear ribonucleoprotein
(snRNP) biogenesis. The marker protein for CBs is coilin. In addition to snRNPs, coilin and other factors, canonical CBs contain
the survivor of motor neuron protein (SMN). SMN can also localize to Gems. Considering the important role that coilin plays
in the formation and composition of CBs, we tested the splicing efficiency of several cell lines that vary in regards to coilin
level and modification using an artificial reporter substrate. We found that cells with both hypomethylated coilin and Gems
are more efficient at reporter splicing compared to cells in which SMN localizes to CBs. In contrast, coilin reduction, which
induces Gem formation, decreases cell proliferation and artificial reporter splicing. These findings demonstrate that coilin
modifications or levels impact artificial reporter splicing, possibly by influencing snRNP biogenesis.
Received 26 December 2007; received after revision 5 February 2008; accepted 7 February 2008 相似文献
915.
Hochrainer K Kroismayr R Baranyi U Binder BR Lipp J 《Cellular and molecular life sciences : CMLS》2008,65(13):2105-2117
Small HERC proteins are defined by the presence of one RCC1-like domain and a HECT domain. Having evolved out of one common ancestor, the four members of the family exhibit a high degree of homology in genomic organization and amino acid sequence, thus it seems possible that they might accomplish similar functions. Here we show that small HERC proteins interact with each other and localize to the same cellular structures, which we identify as late endosomes and lysosomes. We demonstrate interaction of HERC3 with the ubiquitin-like proteins hPLIC-1 and hPLIC-2 and we establish interaction of HERC5 with the metastasis suppressor Nm23B. While hPLIC proteins are not ubiquitinated by HERC3, HERC5 plays an important role in ubiquitination of Nm23B. In summary, although small HERC proteins are highly homologous showing the same subcellular distribution, they undergo different molecular interactions. 相似文献
916.
The ability to produce differentiated cell types at will offers one approach to cell therapy and therefore the treatment and cure of degenerative diseases such as diabetes and liver failure. Until recently it was thought that differentiated cells could only be produced from embryonic or adult stem cells. However, we now know that this is not the case, and there is a growing body of evidence to show that one differentiated cell type can convert into a completely different phenotype (transdifferentiation). Understanding the cellular and molecular basis of transdifferentiation will allow us to reprogram cells for transplantation. This approach will complement the use of embryonic and adult stem cells in the treatment of degenerative disorders. In this review, we will focus on some well-documented examples of transdifferentiation. 相似文献
917.
Molecular and Cellular Basis of Regeneration and Tissue Repair 总被引:3,自引:0,他引:3
Rossi L Salvetti A Batistoni R Deri P Gremigni V 《Cellular and molecular life sciences : CMLS》2008,65(1):16-23
Planarians possess amazing abilities to regulate tissue homeostasis and regenerate missing body parts. These features reside on the presence of a population of pluripotent/totipotent stem cells, the neoblasts, which are considered as the only planarian cells able to proliferate in the asexual strains. Neoblast distribution has been identified by mapping the cells incorporating bromodeoxyuridine, analyzing mitotic figures and using cell proliferation markers. Recently identified molecular markers specifically label subgroups of neoblasts, revealing thus the heterogeneity of the planarian stem cell population. Therefore, the apparent totipotency of neoblasts probably reflects the composite activities of multiple stem cell types. First steps have been undertaken to understand how neoblasts and differentiated cells communicate with each other to adapt the self-renewal and differentiation rates of neoblasts to the demands of the body. Moreover, the introduction of molecular resource database on planarians now paves the way to renewed strategies to understand planarian regeneration and stem cell-related issues. 相似文献
918.
919.
Arachiche A Badirou I Dachary-Prigent J Garcin I Geldwerth-Feniger D Kerbiriou-Nabias D 《Cellular and molecular life sciences : CMLS》2008,65(23):3861-3871
Rapid Ca2+-dependent phospholipid (PL) reorganization (scrambling) at the plasma membrane is a mechanism common to hematopoietic cells
exposing procoagulant phosphatidylserine (PS). The aim of this research was to determine whether activation of the extracellular
signal-regulated kinase (ERK) pathway was required for PL scrambling, based on a single report analyzing both responses induced
by Ca2+ ionophores in megakaryoblastic HEL cells. Ca2+ ionophore-stimulated ERK phosphorylation was induced in platelets without external Ca2+, whereas exogenous Ca2+ entry was crucial for ERK activation in Jurkat T cells. In both cells, membrane scrambling only occurred following Ca2+ entry and was not blocked by inhibiting ERK phosphorylation. Furthermore, ERK proteins are strongly phosphorylated in transformed
B lymphoblastic cell lines, which do not expose PS in their resting state. Overall, the data demonstrated that ERK activation
and membrane scrambling are independent mechanisms.
A. Arachiche, I. Badirou: These authors contributed equally to this work.
Received 18 June 2008; received after revision 24 September 2008; accepted 1 October 2008 相似文献
920.
Olfactory receptors typically exhibit poor plasma membrane localization and functionality when heterologously expressed in
most cell types. It has therefore proven difficult to effectively study olfactory receptor pharmacology and signaling mechanisms
using traditional cell culture systems. Over the past few years, a variety of distinct proteins have been reported to interact
with olfactory receptors and facilitate olfactory receptor trafficking to the plasma membrane in heterologous cells. Advances
in this area have shed significant light on the fundamental factors governing the cell-specific control of olfactory receptor
trafficking. 相似文献