全文获取类型
收费全文 | 258篇 |
免费 | 17篇 |
国内免费 | 43篇 |
专业分类
儿科学 | 6篇 |
妇产科学 | 4篇 |
基础医学 | 52篇 |
口腔科学 | 3篇 |
临床医学 | 48篇 |
内科学 | 47篇 |
皮肤病学 | 2篇 |
神经病学 | 11篇 |
特种医学 | 10篇 |
外科学 | 52篇 |
综合类 | 9篇 |
预防医学 | 16篇 |
眼科学 | 3篇 |
药学 | 51篇 |
肿瘤学 | 4篇 |
出版年
2022年 | 2篇 |
2021年 | 5篇 |
2018年 | 2篇 |
2017年 | 2篇 |
2016年 | 3篇 |
2015年 | 2篇 |
2014年 | 4篇 |
2013年 | 3篇 |
2012年 | 7篇 |
2011年 | 3篇 |
2010年 | 4篇 |
2009年 | 8篇 |
2008年 | 3篇 |
2007年 | 34篇 |
2006年 | 10篇 |
2005年 | 10篇 |
2004年 | 4篇 |
2003年 | 5篇 |
2002年 | 8篇 |
2001年 | 3篇 |
2000年 | 4篇 |
1999年 | 9篇 |
1998年 | 15篇 |
1997年 | 11篇 |
1996年 | 6篇 |
1995年 | 10篇 |
1994年 | 4篇 |
1993年 | 11篇 |
1992年 | 7篇 |
1991年 | 10篇 |
1990年 | 9篇 |
1989年 | 5篇 |
1988年 | 14篇 |
1987年 | 9篇 |
1986年 | 5篇 |
1985年 | 5篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1977年 | 4篇 |
1974年 | 3篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1968年 | 4篇 |
1967年 | 5篇 |
1966年 | 4篇 |
1964年 | 3篇 |
1948年 | 2篇 |
1946年 | 2篇 |
1943年 | 2篇 |
排序方式: 共有318条查询结果,搜索用时 15 毫秒
1.
顺铂聚乳酸微球的药物释放特性及肝动脉栓塞研究 总被引:5,自引:0,他引:5
对顺铂聚乳酸微球进行了体外药物释放和家犬肝动脉栓塞研究。该微球粒径范围为50~200μm,平均粒径为115.76±35.94μm,顺铂含量为37.16%(W/W);体外药物释放机制符合Higuchi方程;肝动脉栓塞后8h,肝组织顺铂浓度高达21.55±12.18μg/g,明显高于肝动脉灌注顺铂组:3.16±0.09μg/g(P<0.05);肝动脉栓塞组的顺铂血浓峰值、各取血点浓度及曲线下面积AUC皆低于肝动脉灌注顺铂组。可望达到提高栓塞部位的药物疗效,降低全身毒副反应的作用。 相似文献
2.
3.
R J Venable 《The Journal of family practice》1992,34(2):201-204
A case of life-threatening angioedema occurring after 13 months of enalapril therapy is reported. Clinicians should be aware that such severe reactions can occur, even after long-term therapy. Patients who take angiotensin-converting enzyme inhibitors should be carefully questioned during each follow-up examination concerning angioedema symptoms. 相似文献
4.
Jonathan Larkin Ling Jin Mark Farmen Daryl Venable Ying Huang Seng-Lai Tan John I Glass 《Journal of interferon & cytokine research》2003,23(5):247-257
The use of type I interferon (IFN), in combination with ribvirin, to treat chronic hepatitis C virus (HCV) infection has many drawbacks that prevent widespread application, ultimately leading to a significant unmet clinical need. Potential improvements in IFN therapy through targeted delivery, molecular alteration, and combination with other agents are ongoing in an attempt to decrease adverse effects and increase efficacy. In this report, the HCV replicon cell culture system was used to assess potential synergistic antiviral effects of multiple IFN species when administered in combination. Quantitative analysis of HCV replicon RNA by TaqMan (PE Applied Biosystems, Foster City, CA) and qualitative analysis of HCV protein expression were used to measure the antiviral efficacy of individual and combination IFN treatments, and synergistic responses of IFN combinations were determined through statistical analysis of the TaqMan results. We found that when administered simultaneously, type I/II IFN combinations (IFN-alpha2b + IFN-gamma or IFN-beta + IFN-gamma) resulted in dramatic antiviral synergy, whereas a type I/I combination (IFN-alpha2b + IFN-beta) demonstrated a slightly antagonistic profile. The synergistic effect is likely due to differential cell surface receptors and signaling pathways employed by types I and II IFNs. Conversely, all type I IFN species bind the same receptor and signal through similar pathways, possibly accounting for the nearly additive response observed. In support of this hypothesis, IFN treatment resulted in differential induction of Stat1 phosphorylation at Tyr 701. In conclusion, simultaneous type I/II IFN combination treatment may allow an overall decreased effective IFN dose, which may reduce the side effect profiles that hinder current therapy. 相似文献
5.
Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group 总被引:5,自引:0,他引:5
Haines JL; Terwedow HA; Burgess K; Pericak-Vance MA; Rimmler JB; Martin ER; Oksenberg JR; Lincoln R; Zhang DY; Banatao DR; Gatto N; Goodkin DE; Hauser SL 《Human molecular genetics》1998,7(8):1229-1234
Multiple sclerosis (MS) is a demyelinating autoimmune disease of the
central nervous system. While its etiology is not well understood, genetic
factors are clearly involved. Until recently, most genetic studies in MS
have been association studies using the case-control design testing
specific candidate genes and studying only sporadic cases. The only
consistently replicated finding has been an association with the HLA-DR2
allele within the major histocompatibility complex (MHC) on chromosome 6.
Using the genetic linkage design, however, evidence for and against linkage
of the MHC to MS has been found, fostering suggestions that sporadic and
familial MS have different etiologies. Most recently, two of four genomic
screens demonstrated linkage to the MHC, although specific allelic
associations were not tested. Here, a dataset of 98 multiplex families was
studied to test for an association to the HLA-DR2 allele in familial MS and
to determine if genetic linkage to the MHC was due solely to such an
association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta)
in the MHC demonstrated strong genetic linkage (parametric lod scores of
4.60, 2.20 and 1.24, respectively) and a specific association with the
HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results
by HLA-DR2 status showed that the linkage results were limited to families
segregating HLA-DR2 alleles. These results demonstrate that genetic linkage
to the MHC can be explained by the HLA-DR2 allelic association. They also
indicate that sporadic and familial MS share a common genetic
susceptibility. In addition, preliminary calculations suggest that the MHC
explains between 17 and 62% of the genetic etiology of MS. This
heterogeneity is also supported by the minority of families showing no
linkage or association with loci within the MHC.
相似文献
6.
Determination of optimal cryoprotectants and procedures for their addition and removal from human spermatozoa 总被引:9,自引:7,他引:9
The objective was to test the hypothesis that the optimal cryoprotective
agent for cryopreservation of human spermatozoa would be a solute for which
cells have the highest plasma membrane permeability, resulting in the least
amount of volume excursion during its addition and removal. To test this
hypothesis, theoretical simulations were performed using membrane
permeability coefficients to predict optimal procedures for the addition
and removal of a cryoprotectant. Simulations were performed using data from
four different cryoprotectants: (i) glycerol, (ii) dimethyl sulphoxide,
(iii) propylene glycol and (iv) ethylene glycol. Thermodynamic formulations
were applied to determine approaches for the addition and removal of 1 M
and 2 M final concentrations of cryoprotectant, allowing the spermatozoa to
maintain a cell volume within their osmotic tolerance limits. Based on
these data, ethylene glycol was predicted to be optimal for minimizing
volume excursions among the solutes evaluated. These predictions were then
experimentally tested using glycerol as the control cryoprotectant and
ethylene glycol as the experimental cryoprotectant. The results indicate
that there was a higher (P < 0.05) recovery of motile spermatozoa after
cryopreservation when using 1 M ethylene glycol than with 1 M glycerol,
supporting the hypothesis that use of the cryoprotectant for which the cell
has the highest permeability will result in higher cell survival.
相似文献
7.
Calcium ionophore-induced acrosome reaction correlates with fertilization rates in vitro in patients with teratozoospermic semen 总被引:5,自引:3,他引:5
The aim of this study was to determine the relationship between calcium
ionophore A23187-induced acrosome reaction (AR) and sperm fertilizing
ability. Semen samples remaining after preparation for standard IVF were
studied in 109 patients who had sperm concentrations > or =20 x
10(6)/ml. Ionophore-induced AR was performed on motile spermatozoa selected
by centrifugation on a Percoll gradient. Semen analysis was performed using
standard methods. Patients with higher (>50%, n = 76) fertilization
rates had significantly higher ionophore-induced AR than patients with
lower (<50%, n = 33) fertilization rates (49 +/- 14 versus 38 +/- 21%, P
< 0.05). When the data from all patients were analysed by logistic
regression, only the percentage sperm motility in insemination medium and
ionophore-induced AR were significantly related to fertilization rates.
Similar results were also obtained when the data from a subgroup of
patients with poor (<15% normal) sperm morphology were analysed.
However, when patients with normal sperm morphology > or =15% were
analysed separately, only sperm count and the percentage of spermatozoa
with progressive motility in semen were significantly related to
fertilization rates. In conclusion, ionophore- induced AR was significantly
related to fertilization rates in vitro mainly in patients with
teratozoospermic semen. Tests for ionophore- induced AR may provide
additional information about sperm fertilizing ability but may not indicate
specific defects of the physiological AR.
相似文献
8.
Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis 总被引:7,自引:2,他引:7
Li DY; Toland AE; Boak BB; Atkinson DL; Ensing GJ; Morris CA; Keating MT 《Human molecular genetics》1997,6(7):1021-1028
Supravalvular aortic stenosis (SVAS) is an inherited obstructive vascular
disease that affects the aorta, carotid, coronary and pulmonary arteries.
Previous molecular genetic data have led to the hypothesis that SVAS
results from mutations in the elastin gene, ELN. In these studies, the
disease phenotype was linked to gross DNA rearrangements (35 and 85 kb
deletions and a translocation) in three SVAS families. However, gross
rearrangements of ELN have not been identified in most cases of autosomal
dominant SVAS. To define the spectrum of ELN mutations responsible for this
disorder, we refined the genomic structure of human ELN and used this
information in mutational analyses. ELN point mutations co-segregate with
the disease in four familial cases and are associated with SVAS in three
sporadic cases. Two of the mutations are nonsense, one is a single base
pair deletion and four are splice site mutations. In one sporadic case, the
mutation arose de novo. These data demonstrate that point mutations of ELN
cause autosomal dominant SVAS.
相似文献
9.
Guo RJ; Wang Y; Kaneko E; Wang DY; Arai H; Hanai H; Takenoshita S; Hagiwara K; Harris CC; Sugimura H 《Carcinogenesis》1998,19(9):1539-1544
Mutations in the transforming growth factor beta type II receptor
(TGFbetaRII) gene have been detected in several human cancer types
exhibiting microsatellite instability. Using intron primers previously
reported for examination of the entire coding region of the TGFbetaRII
gene, 29 sporadic gastric cancers were screened with non-radioactive single
strand conformation polymorphism and subsequent DNA sequencing analysis.
Mutations of the TGFbetaRII gene were detected in three out of 29 tumors
(10%). Two cases showed deletions in a polyadenine tract in both alleles
and was positively associated with replication error. One case had an
insertion of GA dinucleotide sequence in one allele. Mutations of the
TGFbetaRII gene were restricted to exon 3 and other coding regions were not
affected. Loss of heterozygosity was detected by analyzing a polymorphic
site in intron 2. Three out of nine (33%) informative cases, which were all
of intestinal type and advanced cases, showed loss of heterozygosity but
neither TGFbetaRII mutation nor replication error was found in these cases.
Immunoreactivity of TGFbetaRII in tumor tissues was reduced to a different
extent in the gastric cancer with genetically abnormal transforming growth
factor. Although the numbers studied are small, homozygous (A)10 deletion
or loss of heterozygosity of TGFbetaRII is involved in tumorigenesis and
progression of at least some part of sporadic gastric cancer.
相似文献
10.
Exit from G0 and entry into the cell cycle of cells expressing p21Sdi1 antisense RNA. 总被引:7,自引:0,他引:7
下载免费PDF全文
![点击此处可从《Proceedings of the National Academy of Sciences of the United States of America》网站下载免费的PDF全文](/ch/ext_images/free.gif)