全文获取类型
收费全文 | 8514篇 |
免费 | 816篇 |
国内免费 | 3篇 |
出版年
2023年 | 33篇 |
2022年 | 62篇 |
2021年 | 134篇 |
2020年 | 82篇 |
2019年 | 82篇 |
2018年 | 139篇 |
2017年 | 128篇 |
2016年 | 214篇 |
2015年 | 363篇 |
2014年 | 372篇 |
2013年 | 489篇 |
2012年 | 587篇 |
2011年 | 553篇 |
2010年 | 370篇 |
2009年 | 362篇 |
2008年 | 531篇 |
2007年 | 454篇 |
2006年 | 397篇 |
2005年 | 442篇 |
2004年 | 407篇 |
2003年 | 420篇 |
2002年 | 366篇 |
2001年 | 119篇 |
2000年 | 92篇 |
1999年 | 137篇 |
1998年 | 132篇 |
1997年 | 97篇 |
1996年 | 98篇 |
1995年 | 91篇 |
1994年 | 89篇 |
1993年 | 85篇 |
1992年 | 77篇 |
1991年 | 75篇 |
1990年 | 67篇 |
1989年 | 72篇 |
1988年 | 73篇 |
1987年 | 69篇 |
1986年 | 66篇 |
1985年 | 72篇 |
1984年 | 56篇 |
1983年 | 58篇 |
1982年 | 70篇 |
1981年 | 64篇 |
1980年 | 59篇 |
1979年 | 52篇 |
1978年 | 41篇 |
1977年 | 39篇 |
1976年 | 35篇 |
1975年 | 32篇 |
1973年 | 34篇 |
排序方式: 共有9333条查询结果,搜索用时 46 毫秒
121.
Nathalie Bonnefoy Jane Copsey Michael J. Hynes Mervl A. Davis 《Molecular genetics and genomics : MGG》1995,246(2):223-227
The upstream regulatory region of the amdS gene of Aspergillus nidulans contains a CCAAT sequence known to be important in setting both basal and derepressed levels of expression. We have investigated whether the CCAAT-binding HAP2/3/4 complex of the yeast Saccharomyces cerevisiae can recognise this sequence in an amdS context. Sequences from the 5′ region of amdS were cloned in front of the CYCI-lacZ fusion gene bearing a minimal promoter and transformed into wild-type and hap2 strains of yeast. This study has indicated that amdS sequences are capable of promoting regulated expression of the fusion gene in response to carbon limitation. The yeast HAP2/3/4 complex can recognise the amdS CCAAT sequence and activate expression from this sequence. In addition, the results indicate that other yeast proteins can also regulate expression from the A. nidulans amdS 5′ sequences under carbon-limiting conditions. 相似文献
122.
James R. Brorson Vytautas P. Bindokas Toshi Iwama Charles J. Marcuccilli Jane C. Chisholm Richard J. Miller 《Developmental neurobiology》1995,26(3):325-338
Although a neurotoxic role has been postulated for the β-amyloid protein (βAP), which accumulates in brain tissues in Alzheimer's disease, a precise mechanism underlying this toxicity has not been identified. The peptide fragment consisting of amino acid residues 25 through 35 (βAP25-35), in particular, has been reported to be toxic in cultured neurons. We report that βAP25-35, applied to rat hippocampal neurons in culture, caused reversible and repeatable increases in the intracellular Ca2+ concentration ([Ca2+]i), as measured by fura 2 fluorimetry. Furthermore, βAP25-35 induced bursts of excitatory potentials and action potential firing in individual neurons studied with whole cell current clamp recordings. The βAP25-35–induced [Ca2+]i elevations and electrical activity were enhanced by removal of extracellular Mg2+, and they could be blocked by tetrodotoxin, by non-N-methyl-D -aspartate (NMDA) and NMDA glutamate receptor antagonists, and by the L-type Ca2+ channel antagonist nimodipine. Similar responses of bursts of action potentials and [Ca2+]i increases were evoked by βAP1-40. Responses to βAP25-35 were not prevented by pretreatment with pertussis toxin. Excitatory responses and [Ca2+]i elevations were not observed in cerebellar neuron cultures in which inhibitory synapses predominate. Although the effects of βAP25-35 depended on the activation of glutamatergic synapses, there was no enhancement of kainate- or NMDA-induced currents by βAP25-35 in voltage-clamp studies. We conclude that βAP25-35 enhances excitatory activity in glutamatergic synaptic networks, causing excitatory potentials and Ca2+ influx. This property may explain the toxicity of βAP25–35. © 1995 John Wiley & Sons, Inc. 相似文献
123.
124.
Hillard S. Kaplan Jane B. Lancaster Sara E. Johnson John A. Bock 《Human nature (Hawthorne, N.Y.)》1995,6(4):325-360
Our objective is to test an optimality model of human fertility that specifies the behavioral requirements for fitness maximization
in order (a) to determine whether current behavior does maximize fitness and, if not, (b) to use the specific nature of the behavioral deviations from fitness maximization towards the development of models of evolved
proximate mechanisms that may have maximized fitness in the past but lead to deviations under present conditions. To test
the model we use data from a representative sample of 7,107 men living in Albuquerque, New Mexico, between 1990 and 1993.
The model we test proposes that low fertility in modern settings maximizes number of grandchildren as a result of a trade-off
between parental fertility and next generation fertility. Results do not show the optimization, although the data do reveal
a trade-off between parental fertility and offspring education and income.
We propose that two characteristics of modern economies have led to a period of sustained fertility reduction and to a corresponding
lack of association between income and fertility. The first is the direct link between costs of investment and wage rates
due to the forces of supply and demand for labor in competitive economies. The second is the increasing emphasis on cumulative
knowledge, skills, and technologies in the production of resources. Together they produce historically novel conditions. These
two features of modern economies may interact with evolved psychological and physiological mechanisms governing fertility
and parental investment to produce behavior that maximizes the economic productivity of lineages at the expense of fitness.
If cognitive processes evolved to track diminishing returns to parental investment and if physiological processes evolved
to regulate fertility in response to nutritional state and patterns of breast feeding, we might expect non-adaptive responses
when returns from parental investment do not diminish until extremely high levels are reached. With high economic payoffs
from parental investment, people have begun to exercise cognitive regulation of fertility through contraception and family
planning practices. Those cognitive processes maynot have evolved to handle fitness trade-offs between fertility and parental investment.
A preliminary presentation of this data was published in R. I. M. Dunbar, ed.,Human Reproduction Decisions: Biological and Social Perspectives. New York: St. Martin’s Press, 1995. Support for the research project, “Male Fertility and Parenting in New Mexico,” began
with two seed grants from the University of New Mexico’s Biomedical Research Grants Program, 1988 and 1989, and one from the
University of New Mexico Research Allocations Committee, 1988. Further seed money as well as interim funding came from the
William T. Grant Foundation (#89130589 and #91130501). The major support for the project came from the National Science Foundation
from 1990 to 1993 (#BNS-9011723 and #DBS-911552). Both National Science Foundation grants included Research Experience for
Undergraduates supplements.
Hillard S. Kaplan is an Associate Professor of Anthropology at the University of New Mexico. His earlier research and publications
focused on food sharing, time allocation, parental investment, and reproductive strategies among Ache hunter-gatherers in
Paraguay, Machiguenga and Piro forager-horticulturalists in Peru, and villagers of several ethnicities in Botswana. New research
and theory concern fertility, parental investment, and mating strategies in developed and developing nations. This research
formulates a new theory of reproductive decision-making and the demographic transition, integrating human capital and parental
investment theory in a synthesis of economic and evolutionary approaches.
Jane B. Lancaster is a Professor of Anthropology at the University of New Mexico. Her research and publications are on human
reproductive biology and behavior, especially human parental investment; women’s reproductive biology of pregnancy, lactation,
and child-spacing; and male fertility and investment in children. Current research with Hillard S. Kaplan is on male life
history strategies among a large sample of men in New Mexico. She has coedited three books on human parental investment:School-Age Pregnancy and Parenthood (with B. Hamburg),Parenting across the Life Span (with J. Altmann, A. Rossi, and L. Sherrod), andOffspring Abuse and Neglect (with R. Gelles). She is scientific editor of a quarterly journal,Human Nature: An Interdisciplinary, Biosocial Perspective published by Aldine de Gruyter. She is also a council member of the newly formed Human Behavior and Evolution Society.
John A. Bock is Andrew W. Mellon Post-Doctoral Fellow in Epidemiology and Population Health at the National Centre for Epidemiology
and Population Health, The Australian National University. His research focuses on the allocation of parental investment and
the determinants of children’s activities, integrating aspects of economic and evolutionary theory. He has ongoing field research
with Bantu and Bushmen agro-pastoralists and forager-horticulturalists in the Okavango Delta, Botswana. He is also collaborating
with Lancaster and Kaplan on the determinants of progeny distribution and homosexuality among New Mexican men.
Sara E. Johnson is a Ph.D. candidate at the University of New Mexico. Her major research trajectory focuses on trade-offs
in life history characters. Her research experience includes participation in a study of variation in growth and development
among children in a multi-ethnic community in the Okavango Delta, Botswana, in addition to her dissertation work on individual
variation in growth and mortality among juvenile baboons. She is collaborating with Lancaster and Kaplan on the association
between survival and fertility among Albuquerque men. 相似文献
125.
Abstract. Eragrostis intermedia (Plains lovegrass) is a midheight perennial bunchgrass native to semi-arid grasslands of the southwestern USA, that becomes an abundant and dominant component of these grasslands in areas long protected from livestock grazing. Substantial mortality of plains lovegrass occurred on a large livestock exclosure in southeastern Arizona, after a period of declining precipitation, but only in areas that had not burned in the previous three years. Lovegrass abundance subsequently increased on both undisturbed and burned sites, but remained substantially higher on the burned area. Long-term abundance of plains lovegrass may depend on episodic fire, particularly during periods of reduced precipitation. 相似文献
126.
Cornelis H. Hokke Marc J. H. Roosenboom Jane E. Thomas-Oates Johannis P. Kamerling Johannes F. G. Vliegenthart 《Glycoconjugate journal》1994,11(1):35-41
The disialylated poly-(N-acetyllactosamine)-containingO-linked oligosaccharide alditols, released by alkaline borohydride treatment of the enzymicallyN-deglycosylated β-subunit of equine chorionic chonadotropin, were purified by fast protein liquid chromatography (FPLC) on Mono Q and analysed by fast ion bombardment mass spectrometry (FAB-MS) and1H-NMR spectroscopy. The identified oligosaccharide alditols have the following structure: $$\begin{gathered} Neu5Ac\alpha 2 - 3\left[ {Gal\beta 1 - 4GlcNAc\beta 1 - 3} \right]_{0 - 4} Gal\beta 1 - 4GlcNAc\beta 1 - 6 \hfill \\ \begin{array}{*{20}c} { \backslash } \\ { GalNAc - ol} \\ { /} \\ {Neu5Ac\alpha 2 - 3Gal\beta 1 - 3} \\ \end{array} \hfill \\ \end{gathered}$$ 相似文献
127.
Germ-Line Mutations in the von Hippel–Lindau Tumor-Suppressor Gene Are Similar to Somatic von Hippel–Lindau Aberrations in Sporadic Renal Cell Carcinoma 下载免费PDF全文
Jean M. Whaley Joseph Naglich Lawrence Gelbert Y. Edward Hsia James M. Lamiell Jane S. Green Debra Collins Hartmut P. H. Neumann Jana Laidlaw Fred P. Li Andres J. P. Klein-Szanto Bernd R. Seizinger Nikolai Kley 《American journal of human genetics》1994,55(6):1092-1102
von Hippel–Lindau (VHL) disease is a hereditary tumor syndrome predisposing to multifocal bilateral renal cell carcinomas (RCCs), pheochromocytomas, and pancreatic tumors, as well as angiomas and hemangioblastomas of the CNS. A candidate gene for VHL was recently identified, which led to the isolation of a partial cDNA clone with extended open reading frame, without significant homology to known genes or obvious functional motifs, except for an acidic pentamer repeat domain. To further characterize the functional domains of the VHL gene and assess its involvement in hereditary and nonhereditary tumors, we performed mutation analyses and studied its expression in normal and tumor tissue. We identified germ-line mutations in 39% of VHL disease families. Moreover, 33% of sporadic RCCs and all (6/6) sporadic RCC cell lines analyzed showed mutations within the VHL gene. Both germ-line and somatic mutations included deletions, insertions, splice-site mutations, and missense and nonsense mutations, all of which clustered at the 3' end of the corresponding partial VHL cDNA open reading frame, including an alternatively spliced exon 123 nt in length, suggesting functionally important domains encoded by the VHL gene in this region. Over 180 sporadic tumors of other types have shown no detectable base changes within the presumed coding sequence of the VHL gene to date. We conclude that the gene causing VHL has an important and specific role in the etiology of sporadic RCCs, acts as a recessive tumor-suppressor gene, and appears to encode important functional domains within the 3' end of the known open reading frame. 相似文献
128.
Mismatch Repair Genes on Chromosomes 2p and 3p Account for a Major Share of Hereditary Nonpolyposis Colorectal Cancer Families Evaluable by Linkage 总被引:17,自引:1,他引:16 下载免费PDF全文
Minna Nystrm-Lahti Ramon Parsons Pertti Sistonen Lea Pylkknen Lauri A. Aaltonen Fredrick S. Leach Stanley R. Hamilton Patrice Watson Earlene Bronson Ramon Fusaro Jennifer Cavalieri Jane Lynch Stephen Lanspa Tom Smyrk Patrick Lynch Thomas Drouhard Kenneth W. Kinzler Bert Vogelstein Henry T. Lynch Albert de la Chapelle Pivi Peltomki 《American journal of human genetics》1994,55(4):659-665
Two susceptibility loci for hereditary nonpolyposis colo-rectal cancer (HNPCC) have been identified, and each contains a mismatch repair gene: MSH2 on chromosome 2p and MLH1 on chromosome 3p. We studied the involvement of these loci in 13 large HNPCC kindreds originating from three different continents. Six families showed close linkage to the 2p locus, and a heritable mutation of the MSH2 gene was subsequently found in four. The 2p-linked kindreds included a family characterized by the lack of extracolonic manifestations (Lynch I syndrome), as well as two families with cutaneous manifestations typical of the Muir-Torre syndrome. Four families showed evidence for linkage to the 3p locus, and a heritable mutation of the MLH1 gene was later detected in three. One 3p-linked kindred was of Amerindian origin. Of the remaining three families studied for linkage, one showed lod scores compatible with exclusion of both MSH2 and MLH1, while lod scores obtained in the other two families suggested exclusion of one HNPCC locus (MSH2 or MLH1) but were uninformative for markers flanking the other locus. Our results suggest that mismatch repair genes on 2p and 3p account for a major share of HNPCC in kindreds that can be evaluated by linkage analysis. 相似文献
129.
130.
Ellen C. Breen Ronald A. Ignotz Laura McCabe Janet L. Stein Gary S. Stein Jane B. Lian 《Journal of cellular physiology》1994,160(2):323-335
This study examines the mechanism by which TGF-β1, an important mediator of cell growth and differentiation, blocks the differentiation of normal rat diploid fetal osteoblasts in vitro. We have established that the inability for pre-osteoblasts to differentiate is associated with changes in the expression of cell growth, matrix forming, and bone related genes. These include histone, jun B, c-fos, collagen, fibronectin, osteocalcin, alkaline phosphatase, and osteopontin. Morphologically, the TGF-β1-treated osteoblasts exhibit an elongated, spread shape as opposed to the characteristic cuboidal appearance during the early stages of growth. This is followed by a decrease in the number of bone nodules formed and the amount of calcium deposition. These effects on differentiation can occur without dramatic changes in cell growth if TGF-β1 is given for a short time early in the proliferative phase. However, continuous exposure to TGF-β1 leads to a bifunctional growth response from a negative effect during the proliferative phase to a positive growth effect during the later matrix maturation and mineralization phases of the osteoblast developmental sequence. Extracellular matrix genes, fibronectin, osteopontin and α1(I) collagen, are altered in their expression pattern which may provide an aberrant matrix environment for mineralization and osteoblast maturation and potentiate the TGF-β1 response throughout the course of osteoblast differentiation. The initiation of a TGF-β1 effect on cell growth and differentiation is restricted to the proliferative phase of the culture before the cells express the mature osteoblastic phenotype. Second passage cells that are accelerated to differentiate by the addition of dexamethasone or by seeding cultures at a high density are refractory to TGF-β1. These in vitro results indicate that TGF-β1 exerts irreversible effects at a specific stage of osteoblast phenotype development resulting in a potent inhibition of osteoblast differentiation at concentrations from 0.1 ng/ml. © 1994 Wiley-Liss, Inc. 相似文献