全文获取类型
收费全文 | 6630篇 |
免费 | 640篇 |
国内免费 | 3篇 |
专业分类
7273篇 |
出版年
2022年 | 58篇 |
2021年 | 128篇 |
2020年 | 69篇 |
2019年 | 73篇 |
2018年 | 90篇 |
2017年 | 67篇 |
2016年 | 145篇 |
2015年 | 292篇 |
2014年 | 283篇 |
2013年 | 418篇 |
2012年 | 519篇 |
2011年 | 487篇 |
2010年 | 278篇 |
2009年 | 235篇 |
2008年 | 404篇 |
2007年 | 412篇 |
2006年 | 350篇 |
2005年 | 304篇 |
2004年 | 311篇 |
2003年 | 295篇 |
2002年 | 289篇 |
2001年 | 80篇 |
2000年 | 56篇 |
1999年 | 78篇 |
1998年 | 94篇 |
1997年 | 58篇 |
1996年 | 58篇 |
1995年 | 49篇 |
1994年 | 60篇 |
1993年 | 47篇 |
1992年 | 43篇 |
1991年 | 42篇 |
1990年 | 50篇 |
1989年 | 36篇 |
1988年 | 37篇 |
1986年 | 36篇 |
1985年 | 42篇 |
1984年 | 42篇 |
1983年 | 48篇 |
1982年 | 54篇 |
1981年 | 43篇 |
1980年 | 38篇 |
1979年 | 30篇 |
1978年 | 30篇 |
1976年 | 35篇 |
1975年 | 30篇 |
1974年 | 31篇 |
1973年 | 33篇 |
1971年 | 29篇 |
1969年 | 28篇 |
排序方式: 共有7273条查询结果,搜索用时 15 毫秒
91.
Opposing FGF and retinoid pathways control ventral neural pattern, neuronal differentiation, and segmentation during body axis extension 总被引:10,自引:0,他引:10
Vertebrate body axis extension involves progressive generation and subsequent differentiation of new cells derived from a caudal stem zone; however, molecular mechanisms that preserve caudal progenitors and coordinate differentiation are poorly understood. FGF maintains caudal progenitors and its attenuation is required for neuronal and mesodermal differentiation and to position segment boundaries. Furthermore, somitic mesoderm promotes neuronal differentiation in part by downregulating Fgf8. Here we identify retinoic acid (RA) as this somitic signal and show that retinoid and FGF pathways have opposing actions. FGF is a general repressor of differentiation, including ventral neural patterning, while RA attenuates Fgf8 in neuroepithelium and paraxial mesoderm, where it controls somite boundary position. RA is further required for neuronal differentiation and expression of key ventral neural patterning genes. Our data demonstrate that FGF and RA pathways are mutually inhibitory and suggest that their opposing actions provide a global mechanism that controls differentiation during axis extension. 相似文献
92.
Sensing and signalling in response to oxygen deprivation in plants and other organisms 总被引:2,自引:0,他引:2
AIMS AND SCOPE: All aerobic organisms require molecular di-oxygen (O2) for efficient production of ATP though oxidative phosphorylation. Cellular depletion of oxygen results in rapid molecular and physiological acclimation. The purpose of this review is to consider the processes of low oxygen sensing and response in diverse organisms, with special consideration of plant cells. CONCLUSIONS: The sensing of oxygen deprivation in bacteria, fungi, metazoa and plants involves multiple sensors and signal transduction pathways. Cellular responses result in a reprogramming of gene expression and metabolic processes that enhance transient survival and can enable long-term tolerance to sub-optimal oxygen levels. The mechanism of sensing can involve molecules that directly bind or react with oxygen (direct sensing), or recognition of altered cellular homeostasis (indirect sensing). The growing knowledge of the activation of genes in response to oxygen deprivation has provided additional information on the response and acclimation processes. Conservation of calcium fluxes and reactive oxygen species as second messengers in signal transduction pathways in metazoa and plants may reflect the elemental importance of rapid sensing of cellular restriction in oxygen by aerobic organisms. 相似文献
93.
Previous isothermal titration calorimetry (ITC) and Förster resonance energy transfer studies demonstrated that Escherichia coli HUαβ binds nonspecifically to duplex DNA in three different binding modes: a tighter-binding 34-bp mode that interacts with DNA in large (> 34 bp) gaps between bound proteins, reversibly bending it by 140o and thereby increasing its flexibility, and two weaker, modestly cooperative small site-size modes (10 bp and 6 bp) that are useful for filling gaps between bound proteins shorter than 34 bp. Here we use ITC to determine the thermodynamics of these binding modes as a function of salt concentration, and we deduce that DNA in the 34-bp mode is bent around—but not wrapped on—the body of HU, in contrast to specific binding of integration host factor. Analyses of binding isotherms (8-bp, 15-bp, and 34-bp DNA) and initial binding heats (34-bp, 38-bp, and 160-bp DNA) reveal that all three modes have similar log-log salt concentration derivatives of the binding constants (Ski) even though their binding site sizes differ greatly; the most probable values of Ski on 34-bp DNA or larger DNA are − 7.5 ± 0.5. From the similarity of Ski values, we conclude that the binding interfaces of all three modes involve the same region of the arms and saddle of HU. All modes are entropy-driven, as expected for nonspecific binding driven by the polyelectrolyte effect. The bent DNA 34-bp mode is most endothermic, presumably because of the cost of HU-induced DNA bending, while the 6-bp mode is modestly exothermic at all salt concentrations examined. Structural models consistent with the observed Ski values are proposed. 相似文献
94.
Shashidharan P Paris N Sandu D Karthikeyan L McNaught KS Walker RH Olanow CW 《Journal of neurochemistry》2004,88(4):1019-1025
Childhood-onset dystonia is an autosomal dominant movement disorder associated with a three base pair (GAG) deletion mutation in the DYT1 gene. This gene encodes a novel ATP-binding protein called torsinA, which in the central nervous system is expressed exclusively in neurons. Neither the function of torsinA nor its role in the pathophysiology of DYT1 dystonia is known. In order to better understand the cellular functions of torsinA, we established PC12 cell lines overexpressing wild-type or mutant torsinA and subjected them to various conditions deleterious to cell survival. Treatment of control PC12 cells with an inhibitor of proteasomal activity, an oxidizing agent, or trophic withdrawal, resulted in cell death, whereas PC12 cells that overexpressed torsinA were significantly protected against each of these treatments. Overexpression of mutant torsinA failed to protect cells against trophic withdrawal. These results suggest that torsinA may play a protective role in neurons against a variety of cellular insults. 相似文献
95.
In Drosophila, primordial germ cells (PGCs) are set aside from somatic cells and subsequently migrate through the embryo and associate with somatic gonadal cells to form the embryonic gonad. During larval stages, PGCs proliferate in the female gonad, and a subset of PGCs are selected at late larval stages to become germ line stem cells (GSCs), the source of continuous egg production throughout adulthood. However, the degree of similarity between PGCs and the self-renewing GSCs is unclear. Here we show that many of the genes that are required for GSC maintenance in adults are also required to prevent precocious differentiation of PGCs within the larval ovary. We show that following overexpression of the GSC-differentiation gene bag of marbles (bam), PGCs differentiate to form cysts without becoming GSCs. Furthermore, PGCs that are mutant for nanos (nos), pumilio (pum) or for signaling components of the decapentaplegic (dpp) pathway also differentiate. The similarity in the genes necessary for GSC maintenance and the repression of PGC differentiation suggest that PGCs and GSCs may be functionally equivalent and that the larval gonad functions as a "PGC niche". 相似文献
96.
Random field models for fitness landscapes 总被引:1,自引:0,他引:1
In many cases fitness landscapes are obtained as particular instances of random fields by randomly assigning a large number
of parameters. Models of this type are often characterized reasonably well by their covariance matrices. We characterize isotropic
random fields on finite graphs in terms of their Fourier series expansions and investigate the relation between the covariance
matrix of the random field model and the correlation structure of the individual landscapes constructed from this random field.
Correlation measures are a good characteristic of “rugged landscapes” models as they are closely related to quantities like
the number of local optima or the length of adaptive walks. Our formalism suggests to approximate landscape with known autocorrelation
function by a random field model that has the same correlation structure.
Received: 10 November 1995 / Revised version: 19 February 1996 相似文献
97.
Ruth Young 《Vegetation History and Archaeobotany》1999,8(1-2):31-34
Although archaeobotanical sampling and recovery programmes are a relatively recent implementation in East African archaeology, results from sites where they have been carried out follow a similar trend. This is one of abundant recovery of wood charcoal, but very little in the way of other macroscopic plant remains. Restricted archaeological evidence and ethnographic interviews show the importance of grains, in particular finger millet (Eleusine coracana), for the Bunyoro people of Uganda in pre-colonial times. It has been suggested that one of the possible reasons why finger millet is not being recovered in quantity from archaeological contexts is because the processing of this crop does not involve heating and hence there is not the chance of being deposited in charred form in the archaeological record. Recent ethnographic work on finger millet processing in Uganda shows that it is exposed to heat and potential charring during cleaning and preparation of the grain for either storage or cooking, and this regime is discussed in terms of its activities and products. These findings reinforce the need for archaeobotanists and archaeologists working in this region to look for other possible causes of the scarcity of macroscopic plant remains, and also the importance of considering integrated evidence for agricultural activity on prehistoric sites. 相似文献
98.
Gregory A. Jicha Audrey O' Donnell† Charles Weaver‡ Ruth Angeletti† & Peter Davies‡ 《Journal of neurochemistry》1999,72(1):214-224
Abstract : Immunoaffinity-purified paired helical filaments (PHFs) from Alzheimer's disease (AD) brain homogenates contain an associated protein kinase activity that is able to induce the phosphorylation of PHF proteins on addition of exogenous MgCl2 and ATP. PHF kinase activity is shown to be present in immunoaffinity-purified PHFs from both sporadic and familial AD, Down's syndrome, and Pick's disease but not from normal brain homogenates. Although initial studies failed to show that the kinase was able to induce the phosphorylation of tau, additional studies presented in this article show that only cyclic AMP-dependent protein kinase-pretreated recombinant tau is a substrate for the PHF kinase activity. Deletional mutagenesis, phosphopeptide mapping, and site-directed mutagenesis have identified the PHF kinase phosphorylation sites as amino acids Thr361 and Ser412 in htau40. In addition, the cyclic AMP-dependent protein kinase phosphorylation sites that direct the PHF kinase have been mapped to amino acids Ser356 and Ser409 in htau40. Additional data demonstrate that these hierarchical phosphorylations in the extreme C terminus of tau allow for the incorporation of recombinant tau into exogenously added AD-derived PHFs, providing evidence that certain unique phosphorylations of tau may play a role in the pathogenesis of neurofibrillary pathology in AD. 相似文献
99.
Gjerset RA 《Journal of molecular histology》2006,37(5-7):239-251
The p53/p14ARF/mdm2 stress response pathway plays a central role in mediating cellular responses to oncogene activation, genome instability, and therapy-induced DNA damage. Abrogation of the pathway occurs in most if not all cancers, and may be essential for tumor development. The high frequency with which the pathway is disabled in cancer and the fact that the pathway appears to be incompatible with tumor cell growth, has made it an important point of focus in cancer research and therapeutics development. Recently, Nucleophosmin (NPM, B23, NO38 and numatrin), a multifunctional nucleolar protein, has emerged as a p14ARF binding protein and regulator of p53. While complex formation between ARF and NPM retains ARF in the nucleolus and prevents ARF from activating p53, DNA damaging treatments promote a transient subnuclear redistribution of ARF to the nucleoplasm, where it interacts with mdm2 and promotes p53 activation. The results add support to a recently proposed model in which the nucleolus serves as a p53-uspstream sensor of stress, and where ARF links nucleolar stress signals to nucleoplasmic effectors of the stress response. A better understanding of ARF’s nucleolar interactions could further elucidate the regulation of the p53 pathway and suggest new therapeutic approaches to restore p53 function. 相似文献
100.
Taane G. Clark Kim Mallard Francesc Coll Mark Preston Samuel Assefa David Harris Sam Ogwang Francis Mumbowa Bruce Kirenga Denise M. O’Sullivan Alphonse Okwera Kathleen D. Eisenach Moses Joloba Stephen D. Bentley Jerrold J. Ellner Julian Parkhill Edward C. Jones-López Ruth McNerney 《PloS one》2013,8(12)