全文获取类型
收费全文 | 494篇 |
免费 | 30篇 |
国内免费 | 15篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 32篇 |
妇产科学 | 6篇 |
基础医学 | 57篇 |
口腔科学 | 7篇 |
临床医学 | 60篇 |
内科学 | 82篇 |
皮肤病学 | 18篇 |
神经病学 | 17篇 |
特种医学 | 45篇 |
外科学 | 37篇 |
综合类 | 35篇 |
预防医学 | 20篇 |
眼科学 | 1篇 |
药学 | 86篇 |
肿瘤学 | 35篇 |
出版年
2022年 | 6篇 |
2021年 | 4篇 |
2020年 | 3篇 |
2019年 | 8篇 |
2018年 | 10篇 |
2017年 | 10篇 |
2016年 | 9篇 |
2015年 | 12篇 |
2014年 | 13篇 |
2013年 | 13篇 |
2012年 | 15篇 |
2011年 | 13篇 |
2010年 | 16篇 |
2009年 | 25篇 |
2008年 | 24篇 |
2007年 | 18篇 |
2006年 | 19篇 |
2005年 | 21篇 |
2004年 | 12篇 |
2003年 | 14篇 |
2002年 | 12篇 |
2001年 | 14篇 |
2000年 | 15篇 |
1999年 | 17篇 |
1998年 | 35篇 |
1997年 | 28篇 |
1996年 | 14篇 |
1995年 | 14篇 |
1994年 | 17篇 |
1993年 | 13篇 |
1992年 | 11篇 |
1991年 | 13篇 |
1990年 | 5篇 |
1989年 | 7篇 |
1988年 | 7篇 |
1987年 | 5篇 |
1986年 | 3篇 |
1985年 | 11篇 |
1984年 | 2篇 |
1983年 | 6篇 |
1982年 | 4篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1955年 | 1篇 |
排序方式: 共有539条查询结果,搜索用时 31 毫秒
1.
2.
3.
I J Reynolds K Rothermund S Rajdev A H Fauq A P Kozikowski 《European journal of pharmacology》1992,226(1):53-58
We have monitored the binding of [125I]thienylphencyclidine ([125I]TCP), a novel high affinity radioiodinated ligand that specifically recognizes the NMDA (N-methyl-D-aspartate) receptor in rat brain membranes. [125I]TCP binds with an affinity of about 30 nM, and recognizes a similar number of binding sites to previously employed ligands for this receptor. [125I]TCP binding is characterized by slow association and dissociation rates, and the latter can be modified by the addition of Mg2+ or Zn2+, as previously described for [3H]dizocilpine ([3H]MK801). Other phencyclidine-like ligands displaced [125I]TCP binding with the order of potency dizocilpine greater than thienylphencyclidine greater than ITCP greater than phencyclidine greater than ketamine. The binding of [125I]TCP was also increased by NMDA and glycine-site agonists and inhibited by antagonists of these sites. Surprisingly, however, the polyamines spermidine and spermine did not increase [125I]TCP, even though the polyamine antagonist arcaine was an effective inhibitor of binding. These results show that [125I]TCP is a useful ligand for the NMDA receptor complex that binds to the receptor in a manner that is qualitatively distinct from previously described ligands. 相似文献
4.
Protein kinase C (PKC) has been implicated in enhancing cellular sensitivity to cis-diamminedichloroplatinum(II) (CP). We have synthesized a series of novel analogues of lyngbyatoxin A (7-linalylindolactam V), a natural tumor promoter and a potent activator of PKC, and investigated the effects of these synthetic compounds on PKC activity and the antiproliferative activity of CP. Lyngbyatoxin A was as effective as phorbol esters, such as 12-O-tetradecanoylphorbol-13-acetate, in enhancing the sensitivity of HeLa cells to CP. A 24-h pretreatment of HeLa cells with 1 to 100 nM lyngbyatoxin A caused an approximately 9-fold sensitization to CP. All analogues of lyngbyatoxin A that retained the lactam ring portion of the molecule but contained different hydrophobic substituents at C-7 including indolactam V (ILV), tert-butyl-ILV, or n-hexyl-ILV increased cellular sensitivity to CP in a concentration-dependent manner. Maximum cellular sensitization to CP (9-fold) was seen with 10 nM n-hexyl or tert-butyl compounds, and ILV devoid of any C-7 substitution required higher concentrations (1 microM) for equivalent sensitization. The ability of lyngbyatoxin A analogues to sensitize cells to CP correlated directly with their ability to activate PKC in vitro. Synthetic analogues that lacked the lactam ring structure neither activated PKC nor sensitized cells to CP. The C-9 epi analogue of n-hexyl-ILV was less effective than the corresponding natural stereoisomer in activating PKC as well as sensitizing cells to CP. Exposure of HeLa cells to 100 nM lyngbyatoxin A for 24 h caused a substantial decrease in cellular PKC activity to 20% of the untreated control value, but a similar treatment of cells with n-hexyl- or tert-butyl-ILV led to only a 25% reduction in PKC activity. Concentrations of ILV (e.g. 1 microM) that sensitized HeLa cells to CP caused no down-regulation of PKC. Thus, on the basis of results with these novel lyngbyatoxin A analogues, we conclude that activation but not down-regulation of PKC is necessary for sensitization of HeLa cells to CP. 相似文献
5.
The binding of cocaine, d-amphetamine and dopamine to the site on the dopamine transporter labeled by [3H]mazindol was investigated in rat striatal membranes. N-Ethylmaleimide inhibited about 95% of the specific binding of 5 nM [3H]mazindol in a concentration-dependent manner. The effect of 10 mM N-ethylmaleimide was completely prevented by cocaine (EC50 of 3 microM), but neither 300 microM dopamine nor d-amphetamine afforded any significant protection. On the other hand, high concentrations of cocaine, d-amphetamine and dopamine provided similar protection against inhibition by 0.1 mM N-ethylmaleimide. Taken together these data support the hypothesis that a significant portion of the cocaine binding domain on the transporter is distinct from that of either dopamine or amphetamine. This distinction may be sufficient to allow properly designed drugs to prevent cocaine binding without inhibiting DA transport. 相似文献
6.
AP de Moraes† ÉÂG de Arruda† MAV Vitoriano† MO de Moraes Filho‡ FÂF Bezerra‡ E de Magalhães Holanda§ MEA de Moraes‡ 《Journal of the European Academy of Dermatology and Venereology》2007,21(5):596-601
BACKGROUND: Seborrhoeic dermatitis (SD) is a common dermatosis in human immunodeficiency virus (HIV)-positive patients, many of whom do not respond satisfactorily to conventional topical treatments such as corticosteroids and antifungals. OBJECTIVE: A pilot study to investigate the efficacy and tolerability of pimecrolimus cream 1% in HIV-positive patients with facial SD. METHODS: In a single-centre study, 21 HIV-infected patients with mild to severe SD were treated twice daily with pimecrolimus cream 1% for 14 days. Thereafter, treatment was discontinued and patients followed up for 5 weeks. Skin involvement at baseline and on days 7, 14, 21, 35 and 49 was assessed using a four-point clinical score and digital photography. MAIN OUTCOME MEASURES: Efficacy and safety of pimecrolimus cream 1% treatment and incidence of relapse in the follow-up phase. Results Marked improvement was seen in clinical parameters at day 7, with >or= 90% patients clear of symptoms at day 14. Relapse was observed at day 35 but signs were milder than at baseline. All patients responded to therapy, despite their immunological status. Pimecrolimus did not alter CD4(+) and CD8(+) T-cell counts or viral load during the treatment period. CONCLUSION: Pimecrolimus cream represents a new, effective therapeutic option for facial SD in HIV patients. 相似文献
7.
8.
In-vitro maturation of human germinal vesicle stage oocytes: role of cumulus cells and epidermal growth factor in the culture medium 总被引:21,自引:6,他引:21
Goud PT; Goud AP; Qian C; Laverge H; Van der Elst J; De Sutter P; Dhont M 《Human reproduction (Oxford, England)》1998,13(6):1638-1644
In-vitro maturation (IVM) of oocytes is a promising technique to reduce the
costs and avert the side-effects of gonadotrophin stimulation for in-vitro
fertilization (IVF). The pregnancy rates from oocytes matured in vitro are
much lower than those of in-vivo stimulation cycles indicating that
optimization of IVM remains a challenge. Therefore, we investigated the
effect of supplementation of the medium with gonadotrophins, oestradiol and
epidermal growth factor (EGF) and the effect of retaining or removing the
cumulus cells on nuclear and cytoplasmic maturation of immature oocytes.
Human germinal vesicle (GV) oocytes obtained after gonadotrophin
stimulation for intracytoplasmic sperm injection (ICSI) were cultured in a
complex defined medium either supplemented with gonadotrophins, oestradiol
and physiological concentrations of EGF (2 ng/ml) or gonadotrophins and
oestradiol alone. The cumulus cells were either removed or kept intact. In
GV stage oocytes cultured without cumulus (group I) significantly more
oocytes reached the metaphase II (MII) stage at 30 h in media supplemented
with EGF (64.3 versus 33.9%, P < 0.003). For oocytes cultured with
intact cumulus (group II), more oocytes reached MII at 30 h than in group
I, but there was no difference in medium with or without EGF
supplementation (81.8 and 79.8% respectively). Cytoplasmic maturation of
MII oocytes was judged from their capability to activate and fertilize
after ICSI. In group I, the rates of activation and normal fertilization
were similar. However, in group II, significantly more oocytes underwent
normal fertilization in the EGF-supplemented than the unsupplemented group
(71.7 versus 45.6%, P < 0.05). The cleavage rates of the fertilized
oocytes were similar in the sibling oocyte subgroups cultured with or
without EGF supplementation, but the overall cleavage rates were higher in
cumulus-intact compared to cumulus-denuded oocytes (88.9 versus 47.8%, P
< 0.001). Thus, supplementation of the maturation medium with EGF and
maintenance of the cumulus during culture improve the nuclear and
cytoplasmic maturation of human oocytes in vitro.
相似文献
9.
The effects of co-culture with human fibroblasts on human embryo development in vitro and implantation 总被引:5,自引:0,他引:5
Wetzels AM; Bastiaans BA; Hendriks JC; Goverde HJ; Punt-van der Zalm AP; Verbeet JG; Braat DD 《Human reproduction (Oxford, England)》1998,13(5):1325-1330
In a human in-vitro fertilization (IVF) programme, the effect of co-
culture of embryos with human fibroblasts was evaluated with respect to
pregnancy rate and embryo development. Patients were included in the study
after giving informed written consent. The IVF treatments were randomly
assigned by stratification of both age (<36 versus > or =36 years)
and previous IVF attempts (yes versus no). After fertilization was
established, the zygotes were transferred to a 4-well dish with or without
fibroblasts and cultured for 2 days. On the third day after ovum pick-up
(OPU), cell number and quality [5 (good) to 1 (poor)] of the embryos were
scored and a maximum of three embryos was transferred. Supernumerary
embryos of good quality were cryopreserved. The design of this study was a
group sequential trial with the objective of detecting differences between
pregnancy rates following IVF with conventional incubation or incubation in
co-culture with fibroblasts. This design included one evaluation at
half-way data collection. In the study, 148 patients had an OPU, of whom 77
were allocated to the co-culture group. There was no statistically
significant difference in pregnancy rate, cell number and embryo quality
between the two groups. The ongoing pregnancy rate per embryo transfer was
27% in co-culture and 30% in the conventional culture group. The
implantation rates per transferred embryo were 17 and 18% respectively.
Using a multivariate logistic regression model for the probability of
ongoing pregnancies, the odds ratio of co-culture, adjusted for age and
previous IVF attempts, was not statistically significant. In conclusion,
co-culture with human fibroblasts does not contribute to an improvement of
embryo quality nor to a higher pregnancy rate after IVF in an unselected
group of patients.
相似文献
10.
The UTX gene escapes X inactivation in mice and humans 总被引:7,自引:3,他引:7
Greenfield A; Carrel L; Pennisi D; Philippe C; Quaderi N; Siggers P; Steiner K; Tam PP; Monaco AP; Willard HF; Koopman P 《Human molecular genetics》1998,7(4):737-742
We recently have identified a ubiquitously transcribed mouse Y chromosome
gene, Uty , which encodes a tetratricopeptide repeat (TPR) protein. A
peptide derived from the UTY protein confers H-Y antigenicity on male
cells. Here we report the characterization of a widely transcribed X-linked
homologue of Uty , called Utx , which maps to the proximal region of the
mouse X chromosome and which detects a human X-linked homologue at Xp11.2.
Given that Uty is ubiquitously transcribed, we assayed for Utx expression
from the inactive X chromosome (Xi) in mice and found that Utx escapes X
chromosome inactivation. Only Smcx and the pseudoautosomal Sts gene on the
mouse X chromosome have been reported previously to escape inactivation.
The human UTX gene was also found to be expressed from Xi. We discuss the
significance of these data for our understanding of dosage compensation of
X-Y homologous genes in humans and mice.
相似文献