全文获取类型
收费全文 | 1178篇 |
免费 | 63篇 |
国内免费 | 4篇 |
专业分类
1245篇 |
出版年
2023年 | 7篇 |
2022年 | 16篇 |
2021年 | 25篇 |
2020年 | 27篇 |
2019年 | 14篇 |
2018年 | 31篇 |
2017年 | 29篇 |
2016年 | 56篇 |
2015年 | 34篇 |
2014年 | 62篇 |
2013年 | 72篇 |
2012年 | 71篇 |
2011年 | 58篇 |
2010年 | 38篇 |
2009年 | 37篇 |
2008年 | 47篇 |
2007年 | 40篇 |
2006年 | 44篇 |
2005年 | 42篇 |
2004年 | 33篇 |
2003年 | 23篇 |
2002年 | 29篇 |
2001年 | 24篇 |
2000年 | 28篇 |
1999年 | 24篇 |
1997年 | 14篇 |
1996年 | 16篇 |
1995年 | 6篇 |
1994年 | 11篇 |
1993年 | 7篇 |
1992年 | 13篇 |
1991年 | 13篇 |
1990年 | 14篇 |
1989年 | 12篇 |
1988年 | 17篇 |
1987年 | 10篇 |
1986年 | 18篇 |
1985年 | 17篇 |
1984年 | 20篇 |
1983年 | 7篇 |
1982年 | 7篇 |
1981年 | 6篇 |
1979年 | 10篇 |
1978年 | 10篇 |
1977年 | 8篇 |
1974年 | 9篇 |
1973年 | 11篇 |
1972年 | 6篇 |
1971年 | 12篇 |
1970年 | 10篇 |
排序方式: 共有1245条查询结果,搜索用时 0 毫秒
71.
The status of women, which is relative and multidimensional, has an important bearing on any long-term reduction in fertility. In Indian society, where cohabitation and childbearing are socially sanctioned only after marriage, the length of the first-birth interval affects the completed family size by influencing the spacing and childbearing pattern of a family. This study examines the influence of certain aspects of the status of married women--education, employment, role in family decision making, and age at marriage--along with three socioeconomic variables--per capita income of the family, social position of the household, and the caste system--on the duration of the first-birth interval in an urban Hindu society of the north-east Indian state of Assam. The data were analysed by applying life table and hazard regression techniques. The results indicate that a female's age at marriage, education, current age, role in decision making, and the per capita income of the household are the main covariates that strongly influence the length of the first-birth interval of Hindu females of urban Assam. Of all the covariates studied, a female's education appears to be a key mediating factor, through its influence on her probability of employment outside the home and thereby an earned income and on her role in family decision making. Unlike other Indian communities, the effect of the caste system does not have a significant effect on first-birth timing in this urban Hindu society. 相似文献
72.
A Nath K Conant P Chen C Scott E O Major 《The Journal of biological chemistry》1999,274(24):17098-17102
The pathological correlates of dementia due to human immunodeficiency virus (HIV) infection are glial cell activation and cytokine dysregulation. These findings occur in the setting of small numbers of productively infected cells within the brain. We determined whether exposure of susceptible cells to Tat protein of HIV could result in the production of select proinflammatory cytokines. In a dose-responsive manner, Tat induced interleukin (IL)-1beta production in monocytic cells, while astrocytic cells showed an increase in mRNA for IL-1beta, but had a translation block for IL-1beta protein production. Conversely, IL-6 protein and mRNA productions were strongly induced in astrocytic cells and minimally in monocytic cells. IL-1beta and IL-6 production were independent of tumor necrosis factor-alpha production. An exposure to Tat for a few minutes was sufficient for sustained releases of cytokines for several hours. This prolonged cytokine production is likely maintained by a positive feed back loop of Tat-induced nuclear factor kappaB activation and cytokine production that is independent of extracellular calcium. Thus a transient exposure may be sufficient to initiate a cascade of events resulting in cerebral dysfunction and a "hit and run" approach may be in effect. Hence cross-sectional measurement of viral load in the brain may not be a useful indicator of the role of viral products in the neuropathogenesis of HIV dementia. 相似文献
73.
Genetic admixture of European FRDA genes is the cause of Friedreich ataxia in the Mexican population
Gómez M Clark RM Nath SK Bhatti S Sharma R Alonso E Rasmussen A Bidichandani SI 《Genomics》2004,84(5):779-784
Friedreich ataxia accounts for approximately 75% of European recessive ataxia patients. Approximately 98% of pathogenic chromosomes have large expansions of a GAA triplet repeat in the FRDA gene (E alleles), and strong linkage disequilibrium among polymorphisms spanning the FRDA locus indicates a common origin for all European E alleles. In contrast, we found that only 14 of 151 (9.3%) Mexican Mestizo patients with recessive ataxia were homozygous for E alleles. Analysis of polymorphisms spanning the FRDA locus revealed that all Mestizo E alleles had the common European haplotype, indicating that they share a single origin. Genetic admixture levels were determined, which revealed that the relative contributions to the Mestizo FRDA gene pool by Native American and European genes were 76-87% and 13-24%, respectively, commensurate with the observed low prevalence of Friedreich ataxia in Mestizos. This indicates that Friedreich ataxia in Mexican Mestizos is due to genetic admixture of European mutant FRDA genes in the Native American gene pool that existed prior to contact with Europeans. 相似文献
74.
Nath AK Enciso J Kuniyasu M Hao XY Madri JA Pinter E 《Development (Cambridge, England)》2004,131(10):2485-2496
Nitric oxide (NO) has been demonstrated to mediate events during ovulation, pregnancy, blastocyst invasion and preimplantation embryogenesis. However, less is known about the role of NO during postimplantation development. Therefore, in this study, we explored the effects of NO during vascular development of the murine yolk sac, which begins shortly after implantation. Establishment of the vitelline circulation is crucial for normal embryonic growth and development. Moreover, functional inactivation of the endodermal layer of the yolk sac by environmental insults or genetic manipulations during this period leads to embryonic defects/lethality, as this structure is vital for transport, metabolism and induction of vascular development. In this study, we describe the temporally/spatially regulated distribution of nitric oxide synthase (NOS) isoforms during the three stages of yolk sac vascular development (blood island formation, primary capillary plexus formation and vessel maturation/remodeling) and found NOS expression patterns were diametrically opposed. To pharmacologically manipulate vascular development, an established in vitro system of whole murine embryo culture was employed. During blood island formation, the endoderm produced NO and inhibition of NO (L-NMMA) at this stage resulted in developmental arrest at the primary plexus stage and vasculopathy. Furthermore, administration of a NO donor did not cause abnormal vascular development; however, exogenous NO correlated with increased eNOS and decreased iNOS protein levels. Additionally, a known environmental insult (high glucose) that produces reactive oxygen species (ROS) and induces vasculopathy also altered eNOS/iNOS distribution and induced NO production during yolk sac vascular development. However, administration of a NO donor rescued the high glucose induced vasculopathy, restored the eNOS/iNOS distribution and decreased ROS production. These data suggest that NO acts as an endoderm-derived factor that modulates normal yolk sac vascular development, and decreased NO bioavailability and NO-mediated sequela may underlie high glucose induced vasculopathy. 相似文献
75.
Blackwell KA Sorenson JP Richardson DM Smith LA Suda O Nath K Katusic ZS 《American journal of physiology. Heart and circulatory physiology》2004,287(6):H2448-H2453
Oxidative stress has been implicated as an important mechanism of vascular endothelial dysfunction induced by aging. Previous studies suggested that tetrahydrobiopterin (BH4), an essential cofactor of endothelial NO synthase, could be a molecular target for oxidation. We tested the hypothesis that oxidative stress, in particular oxidation of BH4, may contribute to attenuation of endothelium-dependent relaxation in aged mice. Vasomotor function of isolated carotid arteries was studied using a video dimension analyzer. Vascular levels of BH4 and its oxidation products were measured via HPLC. In aged mice (age, 95 +/- 2 wk), endothelium-dependent relaxation to ACh (10(-5) to 10(-9) M) as well as endothelium-independent relaxation to the NO donor diethylammonium (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA-NONOate, 10(-5) to 10(-9) M) were significantly reduced compared with relaxation detected in young mice (age, 23 +/- 0.5 wk). Incubation of aged mouse carotid arteries with the cell-permeable SOD mimetic Mn(III)tetra(4-benzoic acid)porphyrin chloride normalized relaxation to ACh and DEA-NONOate. Furthermore, production of superoxide anion in aorta and serum levels of amyloid P component, which is the murine analog of C-reactive protein, was increased in old mice. In aorta, neither the concentration of BH4 nor the ratio of reduced BH4 to the oxidation products were different between young and aged mice. Our results demonstrate that in mice, aging impairs relaxation mediated by NO most likely by increased formation of superoxide anion. Oxidation of BH4 does not appear to be an important mechanism underlying vasomotor dysfunction in aged mouse arteries. 相似文献
76.
Calpains are Ca2+-dependent intracellular cysteine proteases, including the ubiquitously expressed micro- and m-calpains. Both are heterodimers, consisting of a distinct catalytic subunit and a common regulatory subunit. We describe cloning and sequencing of the calpain small (regulatory) subunit (cpns) cDNA from rainbow trout. This represents the first fish and lower vertebrate full cDNA of cpns. The rainbow trout cpns cDNA was used to retrieve the zebra fish and Japanese flounder homologues. We present evidence that fish cpns, unlike the conventional mammalian predominant isoform, cpnsl, is lacking the glycine-rich region of domain V. Because the glycine-rich region is known to play a role in membrane targeting, this divergent cpns suggests potentially different functional and activation mechanisms of the fish calpain system. A phylogenetic tree for the cpns gene superfamily has been constructed and the evolution of cpns considered. 相似文献
77.
Microtubule-dependent movement of late endocytic vesicles in vitro: requirements for Dynein and Kinesin 下载免费PDF全文
Bananis E Nath S Gordon K Satir P Stockert RJ Murray JW Wolkoff AW 《Molecular biology of the cell》2004,15(8):3688-3697
Our previous studies demonstrated that fluorescent early endocytic vesicles prepared from rat liver after injection of Texas red asialoorosomucoid contain asialoglycoprotein and its receptor and move and undergo fission along microtubules using kinesin I and KIFC2, with Rab4 regulating KIFC2 activity (J. Cell Sci. 116, 2749, 2003). In the current study, procedures to prepare fluorescent late endocytic vesicles were devised. In addition, flow cytometry was utilized to prepare highly purified fluorescent endocytic vesicles, permitting validation of microscopy-based experiments as well as direct biochemical analysis. These studies revealed that late vesicles bound to and moved along microtubules, but in contrast to early vesicles, did not undergo fission. As compared with early vesicles, late vesicles had reduced association with receptor, Rab4, and kinesin I but were highly associated with dynein, Rab7, dynactin, and KIF3A. Dynein and KIF3A antibodies inhibited late vesicle motility, whereas kinesin I and KIFC2 antibodies had no effect. Dynamitin antibodies prevented the association of late vesicles with microtubules. These results indicate that acquisition and exchange of specific motor and regulatory proteins characterizes and may regulate the transition of early to late endocytic vesicles. Flow cytometric purification should ultimately facilitate detailed proteomic analysis and mapping of endocytic vesicle-associated proteins. 相似文献
78.
Goswami S Chatterjee S Bhattacharyya SN Basu S Adhya S 《Nucleic acids research》2003,31(19):5552-5559
Import of nucleus-encoded tRNAs into the mitochondria of the kinetoplastid protozoon Leishmania involves recognition of specific import signals by the membrane-bound import machinery. Multiple signals on different tRNA domains may be present, and further, importable RNAs interact positively (Type I) or negatively (Type II) with one another at the inner membrane in vitro. By co-transfection assays, it is shown here that tRNATyr (Type I) transiently stimulates the rate of entry of tRNAIle (Type II) into Leishmania mitochondria in transfected cells, and conversely, is inhibited by tRNAIle. Truncation and mutagenesis experiments led to the co-localization of the effector and import activities of tRNATyr to the D domain, and those of tRNAIle to the variable region–T domain (V-T region), indicating that both activities originate from a single RNA–receptor interaction. A third tRNA, human tRNALys, is imported into Leishmania mitochondria in vitro as well as in vivo. This tRNA has Type I and Type II motifs in the D domain and the V-T region, respectively, and shows both Type I and Type II effector activities. Such dual-type tRNAs may interact simultaneously with the Type I and Type II binding sites of the inner membrane import machinery. 相似文献
79.
Inactivation of Cyanobacterial Nitrogenase After Exposure to Ultraviolet-B Radiation 总被引:2,自引:0,他引:2
Exposure of the N2-fixing cyanobacterium Anabaena BT2 to ultraviolet-B radiation (2.5 W m−2) for 30 min resulted in complete loss of nitrogenase activity but 100% cell killing occurred only after a 90-min exposure.
Inactivation of nitrogenase activity was not specific to Anabaena BT2; other species also showed a similar effect. The time required for 100% killing and inactivation of nitrogenase activity
differed in various species, and this difference may be ascribed to the presence of different levels of UV-B protection mechanisms
in individual species. Inhibition of nitrogenase activity was immediate, since exposure of cultures to UV-B for as little
as 5 min elicited some inhibition of activity. The activity of UV-B-inhibited nitrogenase did not recover upon transfer of
exposed cells to fluorescent light, suggesting that the inhibition may be due to specific inactivation of the enzyme. By employment
of inhibitors of protein synthesis and PS-II activity, it was demonstrated that restoration of nitrogenase activity in a UV-B-treated
culture occurred by fresh synthesis of nitrogenase polypeptide. Our findings suggest that estimation of nitrogenase activity
in diazotrophic species may be used as a marker enzyme for assessing the impact of UV-B radiation.
Received: 13 June 2002 / Accepted: 22 July 2002 相似文献
80.
Effect of ovariectomy and estrogen supplementation on brain acetylcholinesterase activity and passive-avoidance learning in rats 总被引:2,自引:0,他引:2
Das A Dikshit M Srivastava SR Srivastava UK Nath C 《Canadian journal of physiology and pharmacology》2002,80(9):907-914
The effect of ovariectomy and estrogen treatment on the brain acetylcholinesterase activity and cognition in rats was investigated in this study. Ovariectomized and nonovariectomized rats were treated subcutaneously with estradiol dipropionate for 8 d. In the single-trial, passive-avoidance test all the groups showed significant learning and retention of memory as evident by the increase in transfer latency time in trial 2 as compared with trial 1. No-transfer response was significantly increased in the estradiol-dipropionate-treated ovariectomized (80%) and nonovariectomized (60%) group as compared with the ovariectomized (30%) group. Specific activity of acetylcholinesterase was assayed spectrophotometrically in salt-soluble and detergent-soluble fractions of various brain areas: frontal cortex, cerebral cortex, striatum, hippocampus and hypothalamus, thalamus, pons, medulla, and cerebellum. The effect of ovariectomy and estradiol dipropionate was varied in both fractions of these brain areas. Estradiol dipropionate treatment could restore the acetylcholinesterase activity to the control level only in the detergent-soluble fraction of hypothalamus and salt-soluble fraction of hypothalamus, thalamus, and medulla in ovariectomized rats. The results indicate that ovariectomy alters acetylcholinesterase activity in the brain areas but not in a uniform manner and affects only qualitative aspects of cognitive function, which could be improved by estrogen supplementation. 相似文献