全文获取类型
收费全文 | 2262篇 |
免费 | 135篇 |
国内免费 | 24篇 |
专业分类
耳鼻咽喉 | 36篇 |
儿科学 | 70篇 |
妇产科学 | 111篇 |
基础医学 | 265篇 |
口腔科学 | 58篇 |
临床医学 | 168篇 |
内科学 | 458篇 |
皮肤病学 | 41篇 |
神经病学 | 172篇 |
特种医学 | 221篇 |
外科学 | 233篇 |
综合类 | 4篇 |
一般理论 | 1篇 |
预防医学 | 174篇 |
眼科学 | 14篇 |
药学 | 159篇 |
中国医学 | 5篇 |
肿瘤学 | 231篇 |
出版年
2023年 | 10篇 |
2022年 | 16篇 |
2021年 | 57篇 |
2020年 | 21篇 |
2019年 | 29篇 |
2018年 | 38篇 |
2017年 | 26篇 |
2016年 | 32篇 |
2015年 | 25篇 |
2014年 | 47篇 |
2013年 | 67篇 |
2012年 | 100篇 |
2011年 | 107篇 |
2010年 | 58篇 |
2009年 | 50篇 |
2008年 | 85篇 |
2007年 | 99篇 |
2006年 | 69篇 |
2005年 | 90篇 |
2004年 | 95篇 |
2003年 | 77篇 |
2002年 | 64篇 |
2001年 | 70篇 |
2000年 | 75篇 |
1999年 | 49篇 |
1998年 | 60篇 |
1997年 | 56篇 |
1996年 | 39篇 |
1995年 | 43篇 |
1994年 | 31篇 |
1993年 | 19篇 |
1992年 | 55篇 |
1991年 | 44篇 |
1990年 | 45篇 |
1989年 | 80篇 |
1988年 | 56篇 |
1987年 | 56篇 |
1986年 | 55篇 |
1985年 | 53篇 |
1984年 | 28篇 |
1983年 | 31篇 |
1982年 | 24篇 |
1981年 | 22篇 |
1980年 | 27篇 |
1979年 | 23篇 |
1978年 | 15篇 |
1977年 | 13篇 |
1976年 | 17篇 |
1973年 | 11篇 |
1969年 | 8篇 |
排序方式: 共有2421条查询结果,搜索用时 15 毫秒
21.
Pertussis toxin-catalyzed ADP-ribosylation of Gi-2 and Gi-3 in CHO cells is modulated by inhibitors of intracellular trafficking. 总被引:1,自引:3,他引:1
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
In previous studies, an in vitro ADP-ribosylation assay was developed to quantitatively evaluate the in vivo ADP-ribosylation of eukaryotic target proteins in intact Chinese hamster ovary (CHO) cells by pertussis toxin (PT). Immunoblot analysis identified the two PT-sensitive target proteins in CHO cells as Gi-2 and Gi-3. In this in vitro ADP-ribosylation assay, the ability of PT and ADP-ribosylate Gi-2 and Gi-3 intact CHO cells was not inhibited by cytochalasin D but was inhibited by chloroquine, monensin, and nocodazole. These data implicated the involvement of a cytochalasin D-independent endocytic mechanism, a pH-sensitive step, and microtubules in the ADP-ribosylation of Gi-2 and Gi-3 by PT in intact CHO cells. Preincubation of CHO cells with cycloheximide, at concentrations that reduced protein synthesis by > 95%, did not inhibit the ability of PT to ADP-ribosylate Gi-2 and Gi-3. Control experiments showed that these agents did not affect either the ability of PT to directly ADP-ribosylate the heterotrimeric G protein, Gt, or the binding of PT to CHO cells, except that monensin slightly inhibited the binding of PT to CHO cells. These results are consistent with a model in which PT is internalized by receptor-mediated endocytosis, probably via a cytochalasin D-independent pathway, which involves intracellular trafficking through late endosomes and the Golgi apparatus. An alternative model predicts the presence of a eukaryotic factor that traffics within cells via this pathway and is required by PT to ADP-ribosylate Gi proteins. 相似文献
22.
Expression of the S-1 catalytic subunit of pertussis toxin in Escherichia coli. 总被引:4,自引:5,他引:4
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The S-1 subunit of pertussis toxin was expressed as a fusion protein in a strain of Escherichia coli deficient in protein degradation. The fusion protein reacted with anti-pertussis toxin antibody, and, like authentic pertussis toxin, it ADP-ribosylated a 41,000-molecular-weight membrane protein from human erythrocytes. 相似文献
23.
Development of hatching blastocysts from immature human oocytes following in-vitro maturation and fertilization using a co-culture system 总被引:8,自引:0,他引:8
Hwu YM; Lee RK; Chen CP; Su JT; Chen YW; Lin SP 《Human reproduction (Oxford, England)》1998,13(7):1916-1921
Recently, in-vitro maturation (IVM) of immature human oocytes recovered
from non-stimulated follicles has been applied in the treatment of
infertility. However, in previous reports, very few embryos cultured in
conventional medium have reached the expanded blastocyst stage following
in-vitro maturation and fertilization (IVM/IVF). The objective of this
study was to investigate whether the developmental competence of human
embryos following IVM/IVF could be enhanced by the use of a human ampullary
cell co-culture system. Immature human oocytes were aspirated from small
follicles at Caesarean section and then cultured in medium containing human
menopausal gonadotrophin for 36 to 48 h, followed by insemination. Zygotes
were randomly cultured either in conventional culture medium alone or in
the co-culture system. Of 48 embryos cultured in conventional medium alone,
all arrested at the 2-16- cell stage on day 3 after insemination. Of 46
embryos cultured in the co-culture system, 26 embryos (56.5%) arrested at
the 2-16-cell stage. Six embryos (13%) developed to the morula stage.
Fourteen embryos (30.4%) developed to expanded blastocysts and two
blastocysts were hatching on day 7 after insemination. We conclude that
co-culture significantly enhances the development of blastocysts in embryos
resulting from IVM/IVF.
相似文献
24.
25.
The ratio of 2nd to 4th digit length: a predictor of sperm numbers and concentrations of testosterone, luteinizing hormone and oestrogen 总被引:19,自引:2,他引:19
Manning JT; Scutt D; Wilson J; Lewis-Jones DI 《Human reproduction (Oxford, England)》1998,13(11):3000-3004
The differentiation of the urinogenital system and the appendicular
skeleton in vertebrates is under the control of Hox genes. The common
control of digit and gonad differentiation raises the possibility that
patterns of digit formation may relate to spermatogenesis and hormonal
concentrations. This work was concerned with the ratio between the length
of the 2nd and 4th digit (2D:4D) in humans. We showed that (i) 2D:4D in
right and left hands has a sexually dimorphic pattern; in males mean 2D:4D
= 0.98, i.e. the 4th digit tended to be longer than the 2nd and in females
mean 2D:4D = 1.00, i.e. the 2nd and 4th digits tended to be of equal
length. The dimorphism is present from at least age 2 years and 2D:4D is
probably established in utero; (ii) high 2D:4D ratio in right hands was
associated with germ cell failure in men (P = 0.04); (iii) sperm number was
negatively related to 2D:4D in the right hand (P = 0.004); (iv) in men
testosterone concentrations were negatively related to right hand 2D:4D and
in women and men LH (right hand), oestrogen (right and left hands) and
prolactin (right hand) concentrations were positively correlated with 2D:4D
ratio and (v) 2D:4D ratio in right hands remained positively related to
luteinizing hormone and oestrogen after controlling for sex, age, height
and weight.
相似文献
26.
Rafaella Barbieri Anna Paola Rimondi Daniele Buzzoni Leone Luppi Claudio Nastruzzi Patrizia Orlando Dr Roberto Gambari 《Clinical & experimental metastasis》1989,7(4):417-426
The methylation pattern of the human HLA-DR gene was analyzed in normal breast tissues, breast primary tumors and lymphonodal metastases isolated from patients carrying breast carcinomas. In breast adenomas and also in normal tissues (including breast, muscle, brain, sperm and T- and B-lymphocytes), the HLA-DR gene is hypermethylated at the CCGG and GCGC sites. In all tissues studied, the only constantly unmethylated region is located in the 5 portion of the gene, near the promoter sequence. Further, the results indicate that the HLA-DR gene is hypomethylated in carcinomas and in the relative metastatic lymph nodes. It is suggested that hypomethylation of the human HLA-DR gene could be proposed as a molecular marker of malignant breast tumors. 相似文献
27.
28.
Hart TC; Bowden DW; Bolyard J; Kula K; Hall K; Wright JT 《Human molecular genetics》1997,6(13):2279-2284
Tricho-dento-osseous syndrome (TDO), MIM# 190320, is transmitted as a
highly penetrant autosomal dominant trait that is characterized by variable
clinical expression. The principal clinical features include kinky/curly
hair in infancy, enamel hypoplasia, taurodontism, as well as increased
thickness and density of cranial bones. Possible genetic linkage has been
reported for TDO with the ABO blood group locus, but the gene defect
remains unknown. We have identified four multiplex families (n = 63, 39
affected, 24 unaffected) from North Carolina segregating TDO. We previously
have excluded a major locus for TDO in the ABO region for these families.
Utilizing a genome-wide search strategy, we obtained conclusive evidence
for linkage of the TDO syndrome locus to markers on chromosome 17q21
(D17S791, Z max = 10.54, Theta = 0.00) with no indication of genetic
heterogeneity. Multipoint analysis suggests the TDO locus is located in a 7
cM chromosomal segment flanked by D17S932 and D17S941. This finding
represents the first step towards isolation and cloning of the TDO gene.
Identification of this gene has important implications for understanding
normal and abnormal craniofacial development of hair, teeth and bone.
相似文献
29.
Lactate production in isolated perfused rat lung 总被引:1,自引:0,他引:1
30.
Characterization of the antibody response to the receptor binding domain of botulinum neurotoxin serotypes A and E
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Baldwin MR Tepp WH Pier CL Bradshaw M Ho M Wilson BA Fritz RB Johnson EA Barbieri JT 《Infection and immunity》2005,73(10):6998-7005
Clostridium botulinum neurotoxins (BoNTs) are the most toxic proteins for humans. The current clostridial-derived vaccines against BoNT intoxication have limitations including production and accessibility. Conditions were established to express the soluble receptor binding domain (heavy-chain receptor [HCR]) of BoNT serotypes A and E in Escherichia coli. Sera isolated from mice and rabbits immunized with recombinant HCR/A1 (rHCR/A1) from the classical type A-Hall strain (ATCC 3502) (BoNT/A1) and rHCR/E from BoNT serotype E Beluga (BoNT/E(B)) neutralized the homologous serotype of BoNT but displayed differences in cross-recognition and cross-protection. Enzyme-linked immunosorbent assay and Western blotting showed that alpha-rHCR/A1 recognized epitopes within the C terminus of the HCR/A and HCR/E, while alpha-rHCR/E recognized epitopes within the N terminus or interface between the N and C termini of the HCR proteins. alpha-rHCR/E(B) sera possessed detectable neutralizing capacity for BoNT/A1, while alpha-rHCR/A1 did not neutralize BoNT/E. rHCR/A was an effective immunogen against BoNT/A1 and the Kyoto F infant strain (BoNT/A2), but not BoNT serotype E Alaska (BoNT/E(A)), while rHCR/E(B) neutralized BoNT/E(A), and under hyperimmunization conditions protected against BoNT/A1 and BoNT/A2. The protection elicited by rHCR/A1 to BoNT/A1 and BoNT/A2 and by rHCR/E(B) to BoNT/E(A) indicate that immunization with receptor binding domains elicit protection within sub-serotypes of BoNT. The protection elicited by hyperimmunization with rHCR/E against BoNT/A suggests the presence of common neutralizing epitopes between the serotypes E and A. These results show that a receptor binding domain subunit vaccine protects against serotype variants of BoNTs. 相似文献