全文获取类型
收费全文 | 6396篇 |
免费 | 708篇 |
国内免费 | 1篇 |
专业分类
7105篇 |
出版年
2021年 | 62篇 |
2019年 | 50篇 |
2018年 | 65篇 |
2017年 | 52篇 |
2016年 | 107篇 |
2015年 | 158篇 |
2014年 | 207篇 |
2013年 | 277篇 |
2012年 | 332篇 |
2011年 | 355篇 |
2010年 | 224篇 |
2009年 | 200篇 |
2008年 | 329篇 |
2007年 | 377篇 |
2006年 | 328篇 |
2005年 | 362篇 |
2004年 | 340篇 |
2003年 | 339篇 |
2002年 | 300篇 |
2001年 | 83篇 |
2000年 | 71篇 |
1999年 | 92篇 |
1998年 | 102篇 |
1997年 | 73篇 |
1996年 | 70篇 |
1995年 | 69篇 |
1994年 | 65篇 |
1993年 | 64篇 |
1992年 | 77篇 |
1991年 | 59篇 |
1990年 | 57篇 |
1989年 | 63篇 |
1988年 | 58篇 |
1987年 | 56篇 |
1985年 | 66篇 |
1984年 | 81篇 |
1983年 | 60篇 |
1982年 | 83篇 |
1981年 | 98篇 |
1980年 | 85篇 |
1979年 | 65篇 |
1978年 | 77篇 |
1977年 | 76篇 |
1976年 | 70篇 |
1975年 | 55篇 |
1974年 | 67篇 |
1973年 | 47篇 |
1970年 | 48篇 |
1969年 | 48篇 |
1967年 | 47篇 |
排序方式: 共有7105条查询结果,搜索用时 15 毫秒
91.
Roger A. Hoffman Peter Habeeb Gerald R. Buzzell 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1990,160(3):269-275
Summary Long-term increased or decreased circulating levels of thyroid hormones significantly modify porphyrin concentrations and morphology in the Harderian glands of male and female hamsters. Administration of T3 reduced porphyrin concentrations in females; this treatment or decreasing thyroid hormone levels with KClO4 suppressed the post-castration rise of porphyrins in males. Hypophysectomy led to increased porphyrins in the Harderian glands of males; this rise was suppressed in hypophysectomized males by T3 or T4. In females, hypophysectomy reduced porphyrins which were further reduced by daily administration of T3 or T4. These modifications in the normal females were identical in castrated males. Mitotic activity in the Harderian glands of females was stimulated by KClO4 and by hypophysectomy with or without exogenous T3. In males, castration increased mitotic activity which was suppressed by T3 and exacerbated by KClO4. Increased mitotic activity seemingly follows loss of tissue mass. The data show that thyroid hormones act directly on the Harderian glands rather than indirectly through modification of TSH synthesis/release. Female type glands in males are a consequence of loss of gonadal androgens by castration, or by suppression or loss of thyroid hormones by hypophysectomy or by treatment with KClO4. However, male type glands in females are the result of androgen treatment, and/or increased levels of thyroid hormones via reduced ambient temperatures or of photic input. We conclude that regulation of the Harderian gland appears to be different in the two sexes.Abbreviations
T
3
Triiodothyronine
-
T
4
Thyroxine
-
TSH
Thyroid Stimulating Hormone
-
KClO
4
Potassium Perchlorate
-
h
hours
-
ml
milliliter
-
mg
milligram
-
g
gram
-
male
-
female
-
castrated male
- AP
hypophysectomized
-
CON
Control
-
ALA
delta aminole-vulenic acid
-
HG
Harderian Gland 相似文献
92.
Serum-free culture of enriched mouse anterior and ventral prostatic epithelial cells in collagen gel
Timothy Turner Howard A. Bern Peter Young Gerald R. Cunha 《In vitro cellular & developmental biology. Plant》1990,26(7):722-730
Summary Sustained growth of mouse ventral and anterior prostatic epithelial cells embedded within collagen gel matrix was achieved
in a serum-free medium composed of Dulbecco's modified Eagle's medium and Ham's F12 medium, 1∶1 (vol/vol), supplemented with
bovine serum albumin fraction V, epidermal growth factor, transferrin, cholera toxin, prolactin, 5α-dihydrotestosterone, cortisol,
putrescine, fibroblast growth factor, and a trace element mixture. Three-dimensional growth of prostatic epithelial cells
occurred inside the collagen gel matrix. This serum-free medium allowed cell growth greater than sevenfold over 10 d in culture.
Tissue recombination and cell culture techniques were integrated to demonstrate that cultured cells retained prostatic characteristics.
Following 10 d of culture, epithelial colonies from mouse ventral and anterior prostatic epithelial cell cultures were isolated
and combined with rat fetal urogenital sinus mesenchyme and grown for 4 wk under the renal capsule of intact athymic male
mice. These tissue recombinants showed distinctive prostatic histologic characteristic (alveoli and ducts lined with cuboidal
or columnar epithelium surrounded by stroma). When histologic sections of recombinants were stained with the Hoechst 33258,
epithelial cells of mouse origin were distinguishable from stromal cells of rat origin.
Aided by grants CA-05388 and CA-09041 from the National Institutes of Health, Bethesda, MD, and by M. A. R. C. fellowship
GM08730 to T. T. 相似文献
93.
Quinones may be toxic by a number of mechanisms. including arylation and oxidative stress caused by redox cycling. Using isolated hepatocytes, we have studied the cytotoxicity of four quinones. with differing abilities to arylate cellular nucleophiles and redox cycle. in relation to their effects on cellular pyridine nucleotides. High concentrations of menadione (redox cycles and arylates). 2-hydroxy-1,4-naphthoquinone (neither arylates nor redox cycles via a one electron reduction) 2.3-dimethoxy-1.4-naphthoquinone (a pure redox cycler) and p-benzoquinone (a pure arylator) caused an initial decrease in NAD+ and loss of viability, which was not prevented by 3-aminobenzamide. an inhibitor of poly(ADP-ribose)polymerase. In contrast. 3-aminobenzamide inhibited the loss of NAD' and viability caused by dimethyl sulphate so implicating poly(ADP-ribose)polymerase in its toxicity but not that of the quinones. Non-toxic concentrations of menadione. 2.3-dimethoxy-1.4-naphthoquinone and 2-hydroxy-1.4-naphthoquinone all caused markedly similar changes in cellular pyridine nucleotides. An initial decrease in NAD+ was accompanied by a small. transient increase in NADP+ and followed by a larger. prolonged increase in NADPH and total NADP+ + NADPH. Nucleotide changes were not observed with non-toxic concentrations of p-benzoquinone. Our findings suggest that a primary event in the response of the cell to redox cycling quinones is to bring about an interconversion of pyridine nucleotides. in an attempt to combat the effects of oxidative stress 相似文献
94.
Identification of consensus patterns in unaligned DNA sequences known to be functionally related 总被引:16,自引:0,他引:16
Hertz Gerald Z.; Hartzell George W. III; Stormo Gary D. 《Bioinformatics (Oxford, England)》1990,6(2):81-92
We have developed a method for identifying consensus patternsin a set of unaligned DNA sequences known to bind a common proteinor to have some other common biochemical function. The methodis based on a tnatrix representation of binding site patterns.Each row of the matrix represents one of the four possible bases,each column represents one of the positions of the binding siteand each element is determined by the frequency the indicatedbase occurs at the indicated position. The goal of the methodis to find the most significant matrix-i.e. the one with thelowest probability of occurring by chance-out of all the matricesthat can be formed from the set of related sequences. The reliabilityof the method improves with the number of sequences, while thetime required increases only linearly with the number of sequences.To test this method, we analysed 11 DNA sequences containingpromoters regulated by the Escherichia coli LexA protein. Thematrices we' found were consistent with the known consensussequence, and could distinguish the generally accepted LexAbinding sites from other DNA sequences.
Received on November 6, 1989; accepted on December 20, 1989 相似文献
95.
Kwan-Fu Rex Sheu Noel Y. Calingasan Gerald A. Dienel Harriet Baker Eun-Hee Jung Kwang-Soo Kim †Francesco Paoletti Gary E. Gibson 《Journal of neurochemistry》1996,67(2):684-691
Abstract: Thiamine deficiency impairs oxidative metabolism and causes metabolic encephalopathy. An early reduction in transketolase (TK) activity may be an important pathogenic event. To assess the role of TK, we have delineated the regional/cellular distribution of TK protein and mRNA in adult rat brain in pyrithiamine-induced thiamine deficiency. TK activity declined in both vulnerable and spared regions. Immunoblots showed a parallel reduction of TK protein. With a few exceptions, immunocytochemistry indicated an overall decline of TK immunoreactivity and the decrease was not specific to vulnerable areas. In contrast to the pronounced, general decline of TK protein, in situ hybridization revealed a regional decrease of 0–25% of TK mRNA in thiamine deficiency. Northern blots indicated a similar level of TK mRNA in whole brain in thiamine deficiency. These results show that the decline of TK activity results from a proportional decrease of TK protein, and the deficiency may be due to an instability of TK protein or an inhibition of TK mRNA translation. The lack of correlation of the distribution, and the absence of specific alteration, of TK in affected regions suggest that the reduced TK may not be linked directly to selective vulnerability in thiamine deficiency. 相似文献
96.
Eberhard Fuchs Jan-Christian Wasmuth Gabriele Flügge Gerald Huether Raphael Troost Jürgen Beyer 《Cellular and molecular neurobiology》1996,16(1):21-37
Summary 1. Corticotropin-releasing factor (CRF) is thought to be involved in the regulation of the diurnal activity of the hypothalamus-pituitary-adrenal
(HPA) axis and to act as a neurotransmitter in the brain. To date it is unknown whether the binding sites of the central CRF
system are subject to diurnal variations.
2. We measured the number of CRF binding sites over the course of a complete 24-hr light-dark cycle in the pituitary, amygdala,
bed nucleus of the stria terminalis (BNST), cingulate cortex, visceral cortex, paraventricular nucleus of the hypothalamus,
hippocampus, and locus ceruleus of rats byin vitro receptor autoradiography with iodinated ovine CRF. A 24-hr time course was also established for plasma CRF and corticosterone.
3. The diurnal pattern of plasma CRF does not correlate with the pattern of plasma corticosterone. Within the brain, CRF binding
in the basolateral nucleus of the amygdala showed a U-shaped curve with maximum levels in the morning and a wide hallow between
1500 and 0100. A biphasic profile with a small depression in the afternoon and a more pronounced depression in the second
half of the activity period is characteristic for the other brain areas and the pituitary. The profile for the pituitary correlates
with those for the BNST and the area of the locus ceruleus. Furthermore, the diurnal pattern of CRF binding sites in the BNST
correlates with that of the hippocampus, and the daytime pattern of the visceral cortex is similar to that of both the hippocampus
and the BNST.
4. Since the CRF-binding profiles in the brain and the pituitary clearly differ from the profiles of both plasma CRF and corticosterone,
one may assume that the diurnal pattern of central CRF binding sites is not directly coupled to the activity of the HPA axis. 相似文献
97.
Gerald F. Combs Carlos Garbisu Boihon C. Yee Andrew Yee Donald E. Carlson Nancy R. Smith Andrew C. Magyarosy Terrance Leighton Bob B. Buchanan 《Biological trace element research》1996,52(3):209-225
The bioavailability of selenium (Se) was determined in bacterial strains that reduce selenite to red elemental Se (Seo). A laboratory strain ofBacillus subtilis and a bacterial rod isolated from soil in the vicinity of the Kesterson Reservoir, San Joaquin Valley, CA, (Microbacterium arborescens) were cultured in the presence of 1 mM sodium selenite (Na2SeO3). After harvest, the washed, lyophilizedB. subtilis andM. arborescens samples contained 2.62 and 4.23% total Se, respectively, which was shown to consist, within error, entirely of Seo. These preparations were fed to chicks as supplements to a low-Se, vitamin E-free diet. Three experiments showed that the
Se in both bacteria had bioavailabilities of approx 2% that of selenite. A fourth experiment revealed that gray Seo had a bioavailability of 2% of selenite, but that the bioavailability of red Seo depended on the way it was prepared (by reduction of selenite). When glutathione was the reductant, bioavailability resembled
that of gray Seo and bacterial Se; when ascorbate was the reductant, bioavailability was twice that level (3–4%). These findings suggest that
aerobic bacteria such asB. subtilis andM. arborescens may be useful for the bioremediation of Se-contaminated sites, i.e., by converting selenite to a form of Se with very low
bioavailability. 相似文献
98.
The fate of the anterior neural ridge was studied by following the relative movements of simultaneous spot applications of DiI and DiO from stage 15 through stage 45. These dye movements were mapped onto the neuroepithelium of the developing brain whose shape was gleaned from whole-mount in situs to neural cell adhesion molecule and dissections of the developing nervous system. The result is a model of the cell movements that drive the morphogenesis of the forebrain. The midanterior ridge moves inside and drops down along the most anterior wall of the neural tube. It then pushes forward a bit, rotates ventrally during forebrain flexing, and gives rise to the chiasmatic ridge and anterior hypothalamus. The midanterior plate drops, forming the floor of the forebrain ventricle, and, keeping its place behind the ridge, it gives rise to the posterior hypothalamus or infundibulum. The midlateral anterior ridge slides into the lateral anterior wall of the neural tube and stretches laterally into the optic stalk and retina, and then rotates into a ventral position. The lateral anterior ridge converges to the most anterior part of the dorsal midline during neural tube closure, then rotates anteriorly, and gives rise to telencephalic structures. Whole-mount bromodeoxyuridine labeling at these stages showed that cell division is widespread and relatively uniform throughout the brain during the late neurula and early tailbud stages, but that during late tailbud stages cell division becomes restricted to specific proliferative zones. We conclude that the early morphogenesis of the brain is carried out largely by choreographed cell movements and that later morphogenesis depends on spatially restricted patterns of cell division. © 1995 John Wiley & Sons, Inc. 相似文献
99.
Abraham Dalu Gerald M. Cronin Beverly D. Lyn-Cook Harihara M. Mehendale 《Journal of biochemical and molecular toxicology》1995,10(5):259-264
The resiliency of rats during early postnatal development to CCl4 or to an interactive hepatotoxicity of chlordecone (CD) + CCl4 has been shown to be due to an efficient stimulation of tissue repair. The objective of the current study was to investigate if this is due to efficient expression of transforming growth factor-α (TGF-α) and proto-oncogenes. Postnatally developing (20 day old) and adult (60 day old) male Sprague–Dawley rats were challenged with a single low dose of CCl4 (100 μL/kg, ip) or corn oil. Liver samples were collected during a time course (0–96 h) after the administration of CCl4 and used to examine TGF-α and early (c-fos) and late (H-ras and K-ras) proto-oncogenes mRNA expressions. Significant increases in TGF-α, H-ras, and K-ras gene expressions were evident as early as 12 hours after CCl4 and peaked between 24 and 48 hours in an age-dependent manner as detected by slot-blot analysis. Results of the study revealed three- and twofold increases in TGF-α gene expression in 20 and 60 day old rats, respectively, after CCl4. There were 3.5- and 2.5-fold increases in H-ras and 4.4- and 3.4-fold increases in K-ras in 20 and 60 day old rats, respectively. In contrast, a 10-fold increase in c-fos mRNA expression was evident in 20 day old rats 1 hour after CCl4 treatment, returning to the baseline value by 3 hours, whereas in 60 day old rats, this increase was less than twofold. The overall findings of this study indicate that TGF-α and the early and late proto-oncogene mRNA expressions were enhanced in an age- and time-dependent manner in response to a low dose of CCl4. These results further strengthen the view that the remarkable resiliency of rats to hepatotoxicants during early postnatal development is due to substantial increases in stimulation of hepatocellular regeneration and tissue repair mechanisms, leading to regression of liver injury and recovery. © 1996 John Wiley & Sons, Inc. 相似文献
100.
Efficient strategies for genomic searching using the affected-pedigree-member method of linkage analysis. 总被引:4,自引:3,他引:1
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The affected-pedigree-member (APM) method of linkage analysis is a nonparametric statistic that tests for nonrandom cosegregation of a disease and marker loci. The APM statistic is based on the observation that if a marker locus is near a disease-susceptibility locus, then affected individuals within a family should be more similar at the marker locus than is expected by chance. The APM statistic measures marker similarity in terms of identity by state (IBS) of marker alleles; that is, two alleles are IBS if they are the same, regardless of their ancestral origin. Since the APM statistic measures increased marker similarity, it makes no assumptions concerning how the disease is inherited; this can be an advantage when dealing with complex diseases for which the mode of inheritance is difficult to determine. We investigate here the power of the APM statistic to detect linkage in the context of a genomewide search. In such a search, the APM statistic is evaluated at a grid of markers. Then regions with high APM statistics are investigated more thoroughly by typing more markers in the region. Using simulated data, we investigate various search strategies and recommend an optimal search strategy that maximizes the power to detect linkage while minimizing the false-positive rate and number of markers. We determine an optimal series of three increasing cut-points and an independent criterion for significance. 相似文献