全文获取类型
收费全文 | 15649篇 |
免费 | 1025篇 |
国内免费 | 1332篇 |
出版年
2023年 | 272篇 |
2022年 | 246篇 |
2021年 | 497篇 |
2020年 | 436篇 |
2019年 | 530篇 |
2018年 | 410篇 |
2017年 | 443篇 |
2016年 | 531篇 |
2015年 | 578篇 |
2014年 | 743篇 |
2013年 | 919篇 |
2012年 | 556篇 |
2011年 | 670篇 |
2010年 | 577篇 |
2009年 | 720篇 |
2008年 | 776篇 |
2007年 | 867篇 |
2006年 | 731篇 |
2005年 | 696篇 |
2004年 | 667篇 |
2003年 | 586篇 |
2002年 | 519篇 |
2001年 | 426篇 |
2000年 | 430篇 |
1999年 | 376篇 |
1998年 | 364篇 |
1997年 | 269篇 |
1996年 | 278篇 |
1995年 | 305篇 |
1994年 | 255篇 |
1993年 | 235篇 |
1992年 | 248篇 |
1991年 | 222篇 |
1990年 | 184篇 |
1989年 | 176篇 |
1988年 | 144篇 |
1987年 | 120篇 |
1986年 | 110篇 |
1985年 | 150篇 |
1984年 | 114篇 |
1983年 | 75篇 |
1982年 | 107篇 |
1981年 | 97篇 |
1980年 | 68篇 |
1979年 | 74篇 |
1978年 | 57篇 |
1977年 | 42篇 |
1976年 | 26篇 |
1975年 | 16篇 |
1973年 | 22篇 |
排序方式: 共有10000条查询结果,搜索用时 14 毫秒
991.
During chick liver development, the liver bud arises from the foregut, invaginates into the septum transversum, and elongates along and envelops the ductus venosus. However, the mechanism of liver bud migration is only poorly understood. Here, we demonstrate that a GDNF family ligand involved in neuronal outgrowth and migration, neurturin (NRTN), and its receptor, GFRalpha2, are essential for liver bud migration. In the chick embryo, we found that GFRalpha2 was expressed in the liver bud and that NRTN was expressed in the endothelial cells of the ductus venosus. Inhibition of GFRalpha2 signaling suppressed liver bud elongation along the ductus venous without affecting cell proliferation and apoptosis. Moreover, ectopic expression of NRTN perturbed the directional migration along the ductus venosus, leading to splitting or ectopic branching of the liver. We showed that liver buds selectively migrated toward an NRTN-soaked bead in vitro. These data represent a new model for liver bud migration: NRTN secreted from endothelial cells functions as a chemoattractant to direct the migration of the GFRalpha2-expressing liver bud in early liver development. 相似文献
992.
Epidermal hyperplasia and expansion of the interfollicular stem cell compartment in mutant mice with a C-terminal truncation of Patched1 总被引:1,自引:0,他引:1
Hedgehog (Hh) signaling is conserved from flies to humans and is indispensable in embryogenesis and adulthood. Patched (Ptc) encodes a receptor for Hh ligands and functions as a tumor suppressor. PTCH1 mutations in humans are found in basal cell carcinoma (BCC) and irradiated Ptc1(+/-) mice recapitulate this phenotype. However, due to embryonic lethality associated with the Ptc1 null mutation, its normal function in embryonic and adult skin remains unknown. Here we describe the epidermal phenotypes of a spontaneous and viable allele of Ptc1, Ptc1(mes), in which the C-terminal domain (CTD) is truncated. Ptc1(mes/mes) embryos display normal epidermal and hair follicle development. Postnatal Ptc1(mes/mes) skin displays severe basal cell layer hyperplasia and increased proliferation, while stratification of the suprabasal layers is mostly normal. Interestingly, truncation of the Ptc1 CTD did not result in skin tumors. However, long term labeling studies revealed a greater than three-fold increase in label-retaining cells in the interfollicular epidermis of Ptc1(mes/mes) adults, indicating possible expansion of the epidermal stem cell compartment. Increased expression of regulators of epidermal homeostasis, c-Myc and p63, was also observed in Ptc1(mes/mes) adult skin. These results suggest that the CTD of Ptc1 is involved in regulating epidermal homeostasis in mature skin. 相似文献
993.
Halilagic A Ribes V Ghyselinck NB Zile MH Dollé P Studer M 《Developmental biology》2007,303(1):362-375
We have previously shown that retinoic acid (RA) synthesized by the retinaldehyde dehydrogenase 2 (RALDH2) is required in forebrain development. Deficiency in RA due to inactivation of the mouse Raldh2 gene or to complete absence of retinoids in vitamin-A-deficient (VAD) quails, leads to abnormal morphogenesis of various forebrain derivatives. In this study we show that double Raldh2/Raldh3 mouse mutants have a more severe phenotype in the craniofacial region than single null mutants. In particular, the nasal processes are truncated and the eye abnormalities are exacerbated. It has been previously shown that retinoids act mainly on cell proliferation and survival in the ventral forebrain by regulating SHH and FGF8 signaling. Using the VAD quail model, which survives longer than the Raldh-deficient mouse embryos, we found that retinoids act in maintaining the correct position of anterior and dorsal boundaries in the forebrain by modulating FGF8 anteriorly and WNT signaling dorsally. Furthermore, BMP4 and FGF8 signaling are affected in the nasal region and BMP4 is ventrally expanded in the optic vesicle. At the optic cup stage, Pax6, Tbx5 and Bmp4 are ectopically expressed in the presumptive retinal pigmented epithelium (RPE), while Otx2 and Mitf are not induced, leading to a dorsal transdifferentiation of RPE to neural retina. Therefore, besides being required for survival of ventral structures, retinoids are involved in restricting anterior identity in the telencephalon and dorsal identity in the diencephalon and the retina. 相似文献
994.
Current knowledge about developmental processes in complex organisms has relied almost exclusively on analyses of fixed specimens. However, organ growth is highly dynamic, and visualization of such dynamic processes, e.g., real-time tracking of cell movement and tissue morphogenesis, is becoming increasingly important. Here, we use live imaging to investigate expansion of the embryonic pancreatic epithelium in mouse. Using time-lapse imaging of tissue explants in culture, fluorescently labeled pancreatic epithelium was found to undergo significant expansion accompanied by branching. Quantification of the real-time imaging data revealed lateral branching as the predominant mode of morphogenesis during epithelial expansion. Live imaging also allowed documentation of dynamic beta-cell formation and migration. During in vitro growth, appearance of newly formed beta-cells was visualized using pancreatic explants from MIP-GFP transgenic animals. Migration and clustering of beta-cells were recorded for the first time using live imaging. Total beta-cell mass and concordant aggregation increased during the time of imaging, demonstrating that cells were clustering to form "pre-islets". Finally, inhibition of Hedgehog signaling in explant cultures led to a dramatic increase in total beta-cell mass, demonstrating application of the system in investigating roles of critical embryonic signaling pathways in pancreas development including beta-cell expansion. Thus, pancreas growth in vitro can be documented by live imaging, allowing visualization of the developing pancreas in real-time. 相似文献
995.
Mutation of the Apc1 homologue shattered disrupts normal eye development by disrupting G1 cell cycle arrest and progression through mitosis 总被引:2,自引:0,他引:2
The shattered1 (shtd1) mutation disrupts Drosophila compound eye structure. In this report, we show that the shtd1 eye defects are due to a failure to establish and maintain G1 arrest in the morphogenetic furrow (MF) and a defect in progression through mitosis. The observed cell cycle defects were correlated with an accumulation of cyclin A (CycA) and String (Stg) proteins near the MF. Interestingly, the failure to maintain G1 arrest in the MF led to the specification of R8 photoreceptor cells that undergo mitosis, generating R8 doublets in shtd1 mutant eye discs. We demonstrate that shtd encodes Apc1, the largest subunit of the anaphase-promoting complex/cyclosome (APC/C). Furthermore, we show that reducing the dosage of either CycA or stg suppressed the shtd1 phenotype. While reducing the dosage of CycA is more effective in suppressing the premature S phase entry in the MF, reducing the dosage of stg is more effective in suppressing the progression through mitosis defect. These results indicate the importance of not only G1 arrest in the MF but also appropriate progression through mitosis for normal eye development during photoreceptor differentiation. 相似文献
996.
997.
Lysosomal cathepsins in embryonic programmed cell death 总被引:1,自引:0,他引:1
Zuzarte-Luis V Montero JA Kawakami Y Izpisua-Belmonte JC Hurle JM 《Developmental biology》2007,301(1):205-217
During limb development, expression of cathepsin D and B genes prefigure the pattern of interdigital apoptosis including the differences between the chick and the webbed digits of the duck. Expression of cathepsin L is associated with advanced stages of degeneration. Analysis of Gremlin-/- and Dkk-/- mouse mutants and local treatments with BMP proteins reveal that the expression of cathepsin B and D genes is regulated by BMP signaling, a pathway responsible for triggering cell death. Further cathepsin D protein is upregulated in the preapoptotic mesenchyme before being released into the cytosol, and overexpression of cathepsin D induces cell death in embryonic tissues by a mechanism including mitochondrial permeabilization and nuclear translocation of AIF. Combined inhibition of cathepsin and caspases suggests a redundancy in the apoptotic molecular machinery, providing evidence for compensatory activation mechanisms in the cathepsin pathway when caspases are blocked. It is concluded that lysosomal enzymes are functionally implicated in embryonic programmed cell death. 相似文献
998.
999.
Passport data for Mexico’s Guanajuato State were used to locate the sites where maize was collected in the 1940s and 1950s
in an effort to document and conserve diversity. A map presenting survey points illustrates that collections have occurred
repeatedly in the same locations. Observations of these locations reveal that urbanization and industrialization, not high
yielding varieties, are displacing traditional varieties. Non-linear principal components analysis was used to assess associations
between variables in areas where maize persists. Landraces appear to be associated with mountains and mesas, mixed cropping,
little or no access to irrigation and areas classified as having low agricultural capacity; conversely, landraces have more
commonly been replaced in areas of high agricultural capacity. The areas of high agriculture capacity, located in the riparian
areas and plains, also have been the easiest to develop for urban and industrial use. Increasingly high rates of urbanization
and development in areas of high agriculture capacity will impede the conservation of crop diversity in these areas. 相似文献
1000.
In vivo genetic ablation of the periotic mesoderm affects cell proliferation survival and differentiation in the cochlea 总被引:1,自引:0,他引:1
Tbx1 is required for ear development in humans and mice. Gene manipulation in the mouse has discovered multiple consequences of loss of function on early development of the inner ear, some of which are attributable to a cell autonomous role in maintaining cell proliferation of epithelial progenitors of the cochlear and vestibular apparata. However, ablation of the mesodermal domain of the gene also results in severe but more restricted abnormalities. Here we show that Tbx1 has a dynamic expression during late development of the ear, in particular, is expressed in the sensory epithelium of the vestibular organs but not of the cochlea. Vice versa, it is expressed in the condensed mesenchyme that surrounds the cochlea but not in the one that surrounds the vestibule. Loss of Tbx1 in the mesoderm disrupts this peri-cochlear capsule by strongly reducing the proliferation of mesenchymal cells. The organogenesis of the cochlea, which normally occurs inside the capsule, was dramatically affected in terms of growth of the organ, as well as proliferation, differentiation and survival of its epithelial cells. This model provides a striking demonstration of the essential role played by the periotic mesenchyme in the organogenesis of the cochlea. 相似文献