全文获取类型
收费全文 | 11638篇 |
免费 | 45篇 |
国内免费 | 71篇 |
专业分类
系统科学 | 61篇 |
丛书文集 | 29篇 |
教育与普及 | 21篇 |
理论与方法论 | 32篇 |
现状及发展 | 5438篇 |
研究方法 | 586篇 |
综合类 | 5459篇 |
自然研究 | 128篇 |
出版年
2012年 | 205篇 |
2011年 | 301篇 |
2010年 | 76篇 |
2009年 | 74篇 |
2008年 | 202篇 |
2007年 | 242篇 |
2006年 | 246篇 |
2005年 | 234篇 |
2004年 | 202篇 |
2003年 | 195篇 |
2002年 | 247篇 |
2001年 | 435篇 |
2000年 | 427篇 |
1999年 | 288篇 |
1992年 | 238篇 |
1991年 | 195篇 |
1990年 | 215篇 |
1989年 | 191篇 |
1988年 | 201篇 |
1987年 | 219篇 |
1986年 | 190篇 |
1985年 | 252篇 |
1984年 | 227篇 |
1983年 | 171篇 |
1982年 | 176篇 |
1981年 | 180篇 |
1980年 | 170篇 |
1979年 | 404篇 |
1978年 | 341篇 |
1977年 | 251篇 |
1976年 | 291篇 |
1975年 | 260篇 |
1974年 | 273篇 |
1973年 | 224篇 |
1972年 | 244篇 |
1971年 | 308篇 |
1970年 | 374篇 |
1969年 | 254篇 |
1968年 | 307篇 |
1967年 | 292篇 |
1966年 | 249篇 |
1965年 | 179篇 |
1964年 | 99篇 |
1959年 | 88篇 |
1958年 | 162篇 |
1957年 | 100篇 |
1956年 | 91篇 |
1955年 | 85篇 |
1954年 | 77篇 |
1948年 | 64篇 |
排序方式: 共有10000条查询结果,搜索用时 359 毫秒
841.
The activins (dimers of betaA or betaB subunits, encoded by the genes Inhba and Inhbb, respectively) are TGF-beta superfamily members that have roles in reproduction and development. Whereas mice homozygous for the Inhba-null allele demonstrate disruption of whisker, palate and tooth development, leading to neonatal lethality, homozygous Inhbb-null mice are viable, fertile and have eye defects. To determine if these phenotypes were due to spatiotemporal expression differences of the ligands or disruption of specific ligand-receptor interactions, we replaced the region of Inhba encoding the mature protein with Inhbb, creating the allele Inhbatm2Zuk (hereafter designated InhbaBK). Although the craniofacial phenotypes of the Inhba-null mutation were rescued by the InhbaBK allele, somatic, testicular, genital and hair growth were grossly affected and influenced by the dosage and bioactivity of the allele. Thus, functional compensation within the TGF-beta superfamily can occur if the replacement gene is expressed appropriately. The novel phenotypes in these mice further illustrate the usefulness of insertion strategies for defining protein function. 相似文献
842.
843.
Maleck K Levine A Eulgem T Morgan A Schmid J Lawton KA Dangl JL Dietrich RA 《Nature genetics》2000,26(4):403-410
844.
Calcium signalling in the guidance of nerve growth by netrin-1 总被引:7,自引:0,他引:7
Pathfinding by growing axons in the developing nervous system is guided by diffusible or bound factors that attract or repel the axonal growth cone. The cytoplasmic signalling mechanisms that trigger the responses of the growth cone to guidance factors are mostly unknown. Previous studies have shown that the level and temporal patterns of cytoplasmic Ca2+ can regulate the rate of growth-cone extension in vitro and in vivo. Here we report that Ca2+ also mediates the turning behaviour of the growth cones of cultured Xenopus neurons that are induced by an extracellular gradient of netrin-1, an established diffusible guidance factor in vivo. The netrin-1-induced turning response depends on Ca2+ influx through plasma membrane Ca2+ channels, as well as Ca2+-induced Ca2+ release from cytoplasmic stores. Reduction of Ca2+ signals by blocking either of these two Ca2+ sources converted the netrin-1-induced response from attraction to repulsion. Activation of Ca2+-induced Ca2+ release from internal stores with a gradient of ryanodine in the absence of netrin-1 was sufficient to trigger either attractive or repulsive responses, depending on the ryanodine concentration used. These results support the model that cytoplasmic Ca2+ signals mediate growth-cone guidance by netrin-1, and different patterns of Ca2+ elevation trigger attractive and repulsive turning responses. 相似文献
845.
Williams KA 《Nature》2000,403(6765):112-115
Ion-coupled membrane-transport proteins, or secondary transporters, comprise a diverse and abundant group of membrane proteins that are found in all organisms. These proteins facilitate solute accumulation and toxin removal against concentration gradients using energy supplied by ion gradients across membranes. NhaA is a Na+/H+ antiporter of relative molecular mass 42,000, which is found in the inner membrane of Escherichia coli, and which has been cloned and characterized. NhaA uses the H+ electrochemical gradient to expel Na+ from the cytoplasm, and functions primarily in the adaptation to high salinity at alkaline pH. Most secondary transporters, including NhaA, are predicted to have 12 transmembrane helices. Here we report the structure of NhaA, at 7 A resolution in the membrane plane and at 14 A vertical resolution, determined from two-dimensional crystals using electron cryo-microscopy. The three-dimensional map of NhaA reveals 12 tilted, bilayer-spanning helices. A roughly linear arrangement of six helices is adjacent to a compact bundle of six helices, with the density for one helix in the bundle not continuous through the membrane. The molecular organization of NhaA represents a new membrane-protein structural motif and offers the first insights into the architecture of an ion-coupled transport protein. 相似文献
846.
847.
Nf1;Trp53 mutant mice develop glioblastoma with evidence of strain-specific effects 总被引:11,自引:0,他引:11
Astrocytomas are the leading cause of brain cancer in humans. Because these tumours are highly infiltrative, current treatments that rely on targeting the tumour mass are often ineffective. A mouse model for astrocytoma would be a powerful tool for dissecting tumour progression and testing therapeutics. Mouse models of astrocytoma have been designed to express oncogenic proteins in astrocytes, but have had limited success due to low tumour penetrance or limited tumour progression. We present here a mouse model of astrocytomas involving mutation of two tumour-suppressor genes, Nf1 and Trp53. Humans with mutations in NF1 develop neurofibromatosis type I (NF1) and have increased risk of optic gliomas, astrocytomas and glioblastomas. The TP53 tumour suppressor is often mutated in a subset of astrocytomas that develop at a young age and progress slowly to glioblastoma (termed secondary glioblastomas, in contrast to primary glioblastomas that develop rapidly de novo). This mouse model shows a range of astrocytoma stages, from low-grade astrocytoma to glioblastoma multiforme, and may accurately model human secondary glioblastoma involving TP53 loss. This is the first reported mouse model of astrocytoma initiated by loss of tumour suppressors, rather than overexpression of transgenic oncogenes. 相似文献
848.
849.
A potentially powerful information processing strategy in the brain is to take advantage of the temporal structure of neuronal spike trains. An increase in synchrony within the neural representation of an object or location increases the efficacy of that neural representation at the next synaptic stage in the brain; thus, increasing synchrony is a candidate for the neural correlate of attentional selection. We investigated the synchronous firing of pairs of neurons in the secondary somatosensory cortex (SII) of three monkeys trained to switch attention between a visual task and a tactile discrimination task. We found that most neuron pairs in SII cortex fired synchronously and, furthermore, that the degree of synchrony was affected by the monkey's attentional state. In the monkey performing the most difficult task, 35% of neuron pairs that fired synchronously changed their degree of synchrony when the monkey switched attention between the tactile and visual tasks. Synchrony increased in 80% and decreased in 20% of neuron pairs affected by attention. 相似文献
850.
A clonogenic common myeloid progenitor that gives rise to all myeloid lineages 总被引:153,自引:0,他引:153
Haematopoietic stem cells give rise to progeny that progressively lose self-renewal capacity and become restricted to one lineage. The points at which haematopoietic stem cell-derived progenitors commit to each of the various lineages remain mostly unknown. We have identified a clonogenic common lymphoid progenitor that can differentiate into T, B and natural killer cells but not myeloid cells. Here we report the prospective identification, purification and characterization, using cell-surface markers and flow cytometry, of a complementary clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Common myeloid progenitors give rise to either megakaryocyte/erythrocyte or granulocyte/macrophage progenitors. Purified progenitors were used to provide a first-pass expression profile of various haematopoiesis-related genes. We propose that the common lymphoid progenitor and common myeloid progenitor populations reflect the earliest branch points between the lymphoid and myeloid lineages, and that the commitment of common myeloid progenitors to either the megakaryocyte/erythrocyte or the granulocyte/macrophage lineages are mutually exclusive events. 相似文献