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排序方式: 共有1750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.
Synthesis and structure-activity relationships of new 9-N-alkyl derivatives of 9(S)-erythromycylamine 总被引:4,自引:0,他引:4
H A Kirst J A Wind J P Leeds K E Willard M Debono R Bonjouklian J M Greene K A Sullivan J W Paschal J B Deeter 《Journal of medicinal chemistry》1990,33(11):3086-3094
A series of new 9-N-alkyl derivatives of 9(S)-erythromycylamine has been synthesized by reductive alkylation of erythromycylamine with aliphatic aldehydes and sodium cyanoborohydride. Alternative syntheses employing hydrogenation methods have also been developed. These new 9-N-alkyl derivatives possess excellent antimicrobial activity in vitro and in vivo, especially when administered orally to treat experimental infections in mice. From structure-activity studies, 9-N-(1-propyl)erythromycylamine (LY281389) was selected as the most efficacious derivative. These methods have also been extended to the synthesis of some 9-N,N-dialkyl derivatives of erythromycylamine. 相似文献
3.
Digital radiography of subtle pulmonary abnormalities: an ROC study of the effect of pixel size on observer performance 总被引:3,自引:0,他引:3
Forty conventional radiographs with examples of mild interstitial infiltrates and subtle pneumothoraces and 40 normal studies of the chest were selected and digitized, with pixel sizes of 1.0, 0.5, 0.2, and 0.1 mm. Observer performance tests were carried out using receiver operating characteristic analysis. Conventional radiographs and digitized images were compared. The results indicate that, in such cases, diagnostic accuracy increases significantly as the pixel size is reduced, at least to the 0.1-mm level. We conclude that, for digital systems using screen-film or similar image receptors, use of a pixel size substantially larger than 0.1 mm may result in some loss of diagnostic accuracy. 相似文献
4.
Michael Altmann Beeling C. Wee Keith Willard Denton Peterson Laël C. Gatewood 《Statistics in medicine》1994,13(1):53-60
The authors measure the efficacy of three methods for predicting the time to infection for susceptible individuals in a population undergoing an HIV epidemic. The methods differ in whether they require detailed information of the contact network and whether they require knowledge of the initial source of infection. Efficacy is evaluated using simulations for 20 different contact patterns. Only the risk score that uses both kinds of information accounts for more than 15 per cent of individual variability. The efficacy of this score ranges from 10 per cent in very unstructured populations to 60 per cent for spatially localized contact networks. This improved performance may be explained by the larger fraction of the total variability not due to the disease dynamics. When all variables are dichotomized, the two poorer methods produce odds ratios between 1.4 and 2.3. The odds ratio for the risk score with full information ranges from 2.5 to 17. Risk assessment protocols and intervention programmes are encouraged to assess contact patterns and detect sources of infection. 相似文献
5.
M Debono K E Willard H A Kirst J A Wind G D Crouse E V Tao J T Vicenzi F T Counter J L Ott E E Ose 《The Journal of antibiotics》1989,42(8):1253-1267
A series of 20-deoxo-20-cyclic (alkylamino) derivatives of tylosin, desmycosin, macrocin and lactenocin was prepared by reductive amination of the C-20 aldehyde group. The majority of the compounds were prepared using metal hydrides (sodium cyanoborohydride or sodium borohydride) as the reducing agents and a suitable cyclic alkylamine. Subsequently, a more convenient procedure was developed using formic acid as a reducing agent. The C-20 amino derivatives prepared from desmycosin exhibited good in vitro antimicrobial activity against Pasteurella haemolytica and Pasteurella multocida (MIC range of 0.78 approximately 6.25 micrograms/ml) as well as Mycoplasma species (MIC range of 0.39 approximately 6.25 micrograms/ml). Several derivatives showed excellent oral efficacy against infections caused by P. multocida in chicks. One of these derivatives, 20-deoxo-20-(3,5-dimethylpiperidin-1-yl)desmycosin (tilmicosin or EL-870) was selected for development as a therapeutic agent for pasteurellosis in calves and pigs. 相似文献
6.
Involvement of pp60c-src with two major signaling pathways in human breast cancer. 总被引:14,自引:3,他引:11 下载免费PDF全文
D K Luttrell A Lee T J Lansing R M Crosby K D Jung D Willard M Luther M Rodriguez J Berman T M Gilmer 《Proceedings of the National Academy of Sciences of the United States of America》1994,91(1):83-87
The phosphotyrosine residues of receptor tyrosine kinases serve as unique binding sites for proteins involved in intracellular signaling, which contain SRC homology 2 (SH2) domains. Since overexpression or activation of the pp60c-src kinase has been reported in a number of human tumors, including primary human breast carcinomas, we examined the interactions of the SH2 and SH3 domains of human SRC with target proteins in human carcinoma cell lines. Glutathione S-transferase fusion proteins containing either the SH2, SH3, or the entire SH3/SH2 region of human SRC were used to affinity purify tyrosine-phosphorylated proteins from human breast carcinoma cell lines. We show here that in human breast carcinoma cell lines, the SRC SH2 domain binds to activated epidermal growth factor receptor (EGFR) and p185HER2/neu. SRC SH2 binding to EGFR was also observed in a nontumorigenic cell line after hormone stimulation. Endogenous pp60c-src was found to tightly associate with tyrosine-phosphorylated EGFR. Association of the SRC SH2 with the EGFR was blocked by tyrosyl phosphopeptides containing the sequences surrounding tyrosine-530, the regulatory site in the SRC C terminus, or sequences surrounding the major sites of autophosphorylation in the EGFR. These results raise the possibility that association of pp60c-src with these receptor tyrosine kinases is an integral part of the signaling events mediated by these receptors and may contribute to malignant transformation. 相似文献
7.
Structure-activity studies of 20-deoxo-20-amino derivatives of tylosin-related macrolides 总被引:1,自引:0,他引:1
H A Kirst K E Willard M Debono J E Toth B A Truedell J P Leeds J L Ott A M Felty-Duckworth F T Counter E E Ose 《The Journal of antibiotics》1989,42(11):1673-1683
Reductive amination of the C-20 aldehyde group of tylosin and related macrolides yielded a large series of derivatives with potentially useful antibiotic properties. Evaluation of these new compounds was conducted on the basis of: 1) Broad antimicrobial spectrum in vitro, with particular emphasis on inhibition of Pasteurella multocida and Pasteurella haemolytica; 2) in vivo efficacy, especially when given orally, against P. multocida in experimental infections in chicks; and 3) bioavailability after oral administration to laboratory animals. The most useful activity was found within a series of derivatives produced by reductive amination of desmycosin with secondary amines. 相似文献
8.
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
9.
Y chromosome microdeletions, in azoospermic or near-azoospermic subjects, are located in the AZFc (DAZ) subregion 总被引:9,自引:2,他引:9
Submicroscopic deletions of the Y chromosome and polymorphisms of the
androgen receptor (AR) gene in the X chromosome have been observed in men
with defective spermatogenesis. To further define the subregions/genes in
the Y chromosome causing male infertility and its relationship to
polymorphisms of the AR polyglutamine tract, we screened the genomic DNA of
202 subfertile males and 101 healthy fertile controls of predominantly
Chinese ethnic origin. Y microdeletions were examined with 16
sequence-tagged site (STS) probes, including the RBM and DAZ genes,
spanning the AZFb and AZFc subregions of Yq11, and related to the size of
trinucleotide repeat encoding the AR polyglutamine tract. Y microdeletions
were detected and confirmed in three out of 44 (6.8%) of azoospermic and
three out of 86 (3.5%) severely oligozoospermic patients. No deletions were
detected in any of the patients with sperm counts of >0.5 x 10(6)/ml,
nor in any of the 101 fertile controls. All six affected patients had
almost contiguous Y microdeletions spanning the entire AZFc region
including the DAZ gene. The AZFb region, containing the RBM1 gene, was
intact in five of the six subjects. Y deletions were not found in those
with long AR polyglutamine tracts. Our study, the first in a Chinese
population, suggest a cause and effect relationship between Y
microdeletions in the AZFc region (possibly DAZ), and azoospermia or
near-azoospermia. Y microdeletions and long AR polyglutamine tracts appear
to be independent contributors to male infertility.
相似文献
10.
Dal Zotto L; Quaderi NA; Elliott R; Lingerfelter PA; Carrel L; Valsecchi V; Montini E; Yen CH; Chapman V; Kalcheva I; Arrigo G; Zuffardi O; Thomas S; Willard HF; Ballabio A; Disteche CM; Rugarli EI 《Human molecular genetics》1998,7(3):489-499
We have recently reported isolation of the gene responsible for X- linked
Opitz G/BBB syndrome, a defect of midline development. MID1 is located on
the distal short arm of the human X chromosome (Xp22. 3) and encodes a
novel member of the B box family of zinc finger proteins. We have now
cloned the murine homolog of MID1 and performed preliminary expression
studies during development. Mid1 expression in undifferentiated cells in
the central nervous, gastrointestinal and urogenital systems suggests that
abnormal cell proliferation may underlie the defect in midline development
characteristic of Opitz syndrome. We have also found that Mid1 is located
within the mouse pseudoautosomal region (PAR) in Mus musculus , while it
seems to be X- specific in Mus spretus. Therefore, Mid1 is likely to be a
recent acquisition of the M. musculus PAR. Genetic and FISH analyses also
demonstrated a high frequency of unequal crossovers in the murine PAR,
creating spontaneous deletion/duplication events involving Mid1. These data
provide evidence for the first time that genetic instability of the PAR may
affect functionally important genes. In addition, we show that MID1 is the
first example of a gene subject to X-inactivation in man while escaping it
in mouse. These data contribute to a better understanding of the molecular
content and evolution of the rodent PAR.
相似文献