全文获取类型
收费全文 | 2780篇 |
免费 | 206篇 |
国内免费 | 8篇 |
专业分类
耳鼻咽喉 | 113篇 |
儿科学 | 82篇 |
妇产科学 | 93篇 |
基础医学 | 369篇 |
口腔科学 | 108篇 |
临床医学 | 311篇 |
内科学 | 341篇 |
皮肤病学 | 50篇 |
神经病学 | 256篇 |
特种医学 | 112篇 |
外科学 | 258篇 |
综合类 | 54篇 |
一般理论 | 1篇 |
预防医学 | 186篇 |
眼科学 | 103篇 |
药学 | 205篇 |
肿瘤学 | 352篇 |
出版年
2021年 | 22篇 |
2019年 | 31篇 |
2018年 | 40篇 |
2017年 | 26篇 |
2016年 | 31篇 |
2015年 | 30篇 |
2014年 | 44篇 |
2013年 | 93篇 |
2012年 | 86篇 |
2011年 | 92篇 |
2010年 | 72篇 |
2009年 | 57篇 |
2008年 | 88篇 |
2007年 | 108篇 |
2006年 | 132篇 |
2005年 | 135篇 |
2004年 | 121篇 |
2003年 | 108篇 |
2002年 | 90篇 |
2001年 | 81篇 |
2000年 | 84篇 |
1999年 | 111篇 |
1998年 | 42篇 |
1997年 | 30篇 |
1996年 | 26篇 |
1995年 | 32篇 |
1994年 | 40篇 |
1993年 | 28篇 |
1992年 | 82篇 |
1991年 | 75篇 |
1990年 | 78篇 |
1989年 | 73篇 |
1988年 | 59篇 |
1987年 | 66篇 |
1986年 | 53篇 |
1985年 | 47篇 |
1984年 | 48篇 |
1983年 | 49篇 |
1982年 | 31篇 |
1981年 | 24篇 |
1980年 | 26篇 |
1979年 | 53篇 |
1978年 | 38篇 |
1977年 | 24篇 |
1976年 | 24篇 |
1975年 | 22篇 |
1974年 | 36篇 |
1973年 | 21篇 |
1971年 | 17篇 |
1970年 | 21篇 |
排序方式: 共有2994条查询结果,搜索用时 15 毫秒
21.
van Leth F Huisamen CB Badaro R Vandercam B de Wet J Montaner JS Hall DB Wit FW Lange JM;NN Study Group 《Journal of acquired immune deficiency syndromes (1999)》2005,38(3):296-300
BACKGROUND: The initial rate of plasma HIV-1 RNA (pVL) decline has been proposed as a marker of early efficacy of antiretroviral therapy (ART) and a possible predictor of late efficacy. We compared the rate of pVL decline in patients starting ART with nevirapine (NVP), efavirenz (EFV), or both drugs combined in addition to lamivudine (3TC) and stavudine (d4T). METHODS: Analysis of the viral decay constant (VDc) during the first 2 weeks of treatment in patients enrolled in the 2NN study who remained on allocated treatment. RESULTS: The median VDc (log10 copies per day, [interquartile range]) was similar for NVP (0.30 [0.25-0.36], EFV (0.31 [0.27-0.37]), and NVP + EFV (0.30 [0.27-0.36]). Patients with a baseline pVL >100,000 copies/mL were 8.7 (95% confidence interval [CI]: 6.2-12.3) times more likely to have a VDc >75th percentile. A high VDc was not associated with plasma drug concentration or with a decreased risk of virologic failure at week 48 after the start of therapy (hazard ratio = 0.8, 95% CI: 0.6-1.2). CONCLUSION: NVP, EFV, or NVP + EFV in combination with 3TC and d4T show similar rates of pVL decline during the first 2 weeks of treatment. The VDc with these regimens is not predictive of late virologic efficacy. 相似文献
22.
Around 6% of infants born to mothers taking anticonvulsants have malformations, including neural tube defects, and a further proportion show developmental delay in later childhood. Three commonly used anticonvulsants, carbamazepine, phenytoin and sodium valproate, interfere with folic acid metabolism. We investigated the common 677 C>T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in samples from 57 patients and their parents and 152 controls to determine its contribution to the risk of fetal anticonvulsant syndrome. The 677 C>T mutation frequency was significantly higher in the mothers than in the controls, but there was no significant difference in 677 C>T frequency in the patients or in the fathers. Genotype frequencies in the mothers were significantly different from controls, there being an excess of 677 C>T homozygotes. Amongst the patients, there was an apparent excess of heterozygotes (not statistically significant), and the fathers were not significantly different from controls. Mutation in the MTHFR gene in a mother taking sodium valproate, phenytoin or carbamazepine during pregnancy is associated with fetal anticonvulsant syndrome in her offspring. The skewed distribution of genotypes in the affected children probably reflects the association of fetal anticonvulsant syndrome with the maternal genotype. 相似文献
23.
T S Wallis W G Starkey J Stephen S J Haddon M P Osborne D C Candy 《Journal of medical microbiology》1986,21(1):19-23
Six strains of Salmonella typhimurium (TML, W118, LT7, SL1027, M206 and Thax-1) of known virulence and ability to induce fluid secretion when inoculated into the rabbit ileum were examined for enterotoxin production. Enterotoxic activity, assayed in the rabbit ileal-loop test, was detected in polymyxin-B extracts from all strains (with the possible exception of Thax-1) cultured for 6 h in casamino acid-yeast extract medium. The extracts were inactive in tissue-culture assays with CHO, Y-1 adrenal and Vero cells, and in the infant mouse assay for enterotoxin. There was no correlation between enterotoxigenicity in vitro and the ability of whole organisms to induce fluid secretion in vivo. The significance of these results in relation to salmonellosis is discussed. 相似文献
24.
Joinson C O'Callaghan FJ Osborne JP Martyn C Harris T Bolton PF 《Psychological medicine》2003,33(2):335-344
BACKGROUND: Intellectual impairments are a recognized feature of tuberous sclerosis complex (TSC), but the frequency and degree of intellectual impairments has not been systematically studied in large epidemiological samples using standardized measures. As such, the form of the IQ distribution (uni- or bi-modal) has not been established and the relationship between IQ and other features (e.g. epilepsy history) is poorly delineated. To address these shortcomings, we assessed the intellectual abilities of a large epidemiological sample of individuals with TSC, drawn from the 'Wessex' area of SW England and compared them with the abilities of their unaffected siblings. METHOD: Standardized tests were used to estimate the abilities of 108 (56 males, 52 females, median age = 25, range = 4-75) individuals with TSC and 29 unaffected siblings (14 males, 15 females, median age = 18, range = 6-55). Seizure history was obtained from informants and medical records. RESULTS: Estimated IQ was bi-modally distributed: 55.5% had an IQ in the normal range; 14% had mild to severe impairments: and 30.5% had profound disability (IQ < 21). Forty-four per cent of the individuals with TSC had an IQ < 70. In the subset of normally intelligent individuals with TSC, IQ was normally distributed with a mean of 93.6. This mean was significantly lower than the mean IQ of unaffected siblings (IQ = 105.6). All individuals with learning disability had a history of seizures that usually commenced before 12 months of age and that often presented as infantile spasms. Multivariate analyses indicated that a history of seizures as well as a history of infantile spasms was predictive of the degree of intellectual impairment. CONCLUSIONS: Intellectual abilities were bi-modally distributed in a representative sample of individuals with TSC. The likelihood of impairment was associated with a history of seizures, particularly infantile spasms. The genetic and brain basis of these findings requires further investigation. 相似文献
25.
Gompels MM Lock RJ Morgan JE Osborne J Brown A Virgo PF 《Journal of clinical pathology》2002,55(2):145-147
AIM: To determine the diagnostic efficiency of assays routinely used in the investigation of hereditary angio-oedema. METHODS: Over a four year period, 1144 samples were received for analysis from 907 patients suspected of C1 inhibitor deficiency. Analyses were performed for C4 and C1 inhibitor (functional and immunochemical). Notes were reviewed retrospectively on patients with low serological indicators to determine diagnosis. RESULTS: These are the first data to indicate the sensitivity, specificity, and predictive values of the assays most frequently used to screen for C1 inhibitor deficiency. A combination of low C4 and low C1 inhibitor function has 98% specificity for C1 inhibitor deficiency in this population and a 96% negative predictive value, and is thus a very effective screen. All patients with untreated C1 inhibitor deficiency had a low C4 value. CONCLUSIONS: All patients considered for a diagnosis of C1 inhibitor deficiency should have serum examined to measure both C4 and functional C1 inhibitor. If either is normal at presentation this essentially excludes a diagnosis of C1 inhibitor deficiency. These tests can be performed sequentially. If C4 is normal it is not necessary to proceed to C1 inhibitor analysis. If C1 inhibitor function and C4 are both low then a repeat sample should be obtained to confirm the findings. 相似文献
26.
27.
The Bioperl toolkit: Perl modules for the life sciences 总被引:36,自引:4,他引:36
Stajich JE Block D Boulez K Brenner SE Chervitz SA Dagdigian C Fuellen G Gilbert JG Korf I Lapp H Lehväslaiho H Matsalla C Mungall CJ Osborne BI Pocock MR Schattner P Senger M Stein LD Stupka E Wilkinson MD Birney E 《Genome research》2002,12(10):1611-1618
The Bioperl project is an international open-source collaboration of biologists, bioinformaticians, and computer scientists that has evolved over the past 7 yr into the most comprehensive library of Perl modules available for managing and manipulating life-science information. Bioperl provides an easy-to-use, stable, and consistent programming interface for bioinformatics application programmers. The Bioperl modules have been successfully and repeatedly used to reduce otherwise complex tasks to only a few lines of code. The Bioperl object model has been proven to be flexible enough to support enterprise-level applications such as EnsEMBL, while maintaining an easy learning curve for novice Perl programmers. Bioperl is capable of executing analyses and processing results from programs such as BLAST, ClustalW, or the EMBOSS suite. Interoperation with modules written in Python and Java is supported through the evolving BioCORBA bridge. Bioperl provides access to data stores such as GenBank and SwissProt via a flexible series of sequence input/output modules, and to the emerging common sequence data storage format of the Open Bioinformatics Database Access project. This study describes the overall architecture of the toolkit, the problem domains that it addresses, and gives specific examples of how the toolkit can be used to solve common life-sciences problems. We conclude with a discussion of how the open-source nature of the project has contributed to the development effort. 相似文献
28.
This study compared the career and domestic responsibilities of women physicians whose domestic partners were physicians (WP-Ps) with those of women physicians whose domestic partners were not physicians (WP-NPs). In 1988 the authors surveyed 602 women physicians in a large midwestern city regarding their career and domestic roles; 390 were physicians in training (students and residents), and 212 were physicians in practice (academic medicine and private practice). Overall, 382 (63%) responded; of the 382, 247 (65%) had domestic partners; of these 247, 91 (37%) were WP-Ps and 156 (63%) were WP-NPs. The WP-Ps were found to be twice as likely as the WP-NPs to interrupt their careers to accommodate their partners' careers. The WP-Ps also assumed significantly more domestic responsibilities and worked fewer hours practicing medicine than did the WP-NPs. The 163 women physicians in training (44-48%-of the WP-Ps and 119-76%-of the WP-NPs) demonstrated a more egalitarian division of labor overall, with no significant differences between the WP-Ps and the WP-NPs. The authors recommend that longitudinal studies be undertaken to determine whether women physicians in training continue this trend as they enter the practice of medicine. 相似文献
29.
A. Suto H. Leon Bradlow George Y. C. Wong Michael P. Osborne Nitin T. Telang 《Breast cancer research and treatment》1993,27(3):193-202
Summary The polycyclic aromatic hydrocarbon 7,12-dimethylbenz(a)anthracene (DMBA) is a metabolism-dependent procarcinogen whose tumorigenicity is modified by dietary and endocrine manipulationsin vivo. DMBA initiates molecular and cellular alterations in the mammary tissue, while dietary components and estrogens affect the post-initiational phase of tumorigenic transformation. The mechanism(s) responsible for modulation of tumorigenic transformation remain unclear. This study examines the effects of selected tumor suppressing agents and estradiol (E2) metabolites onin vitro DMBA carcinogenesis utilizing a newly established mouse mammary epithelial cell line C57/MG. Alteration in DNA repair synthesis, metabolism of E2 via the C2- and C16-hydroxylation pathways, and acquisition of anchorage-independent growth were utilized as molecular, endocrine, and cellular biomarkers to quantitate the cellular transformation by DMBA and its modulation by tumor suppressing agents and E2 metabolites. A single 24 hr exposure of 0.78 µM DMBA to C57/MG cells resulted in a 193.9% increase in DNA repair synthesis and a 73.1% decrease in C2/C16 hydroxylation of E2. The DMBA treated C57/MG cells also exhibited increased anchorage-independencein vitro prior to tumorigenesisin vivo. A simultaneous treatment of cells with DMBA and with the highest non-cytotoxic doses of the tumor suppressing agents 5 µM N-(4-hydroxyphenyl) retinamide (HPR), 50 µM indole-3-carbinol (I3C), or 1 µM tamoxifen (TAM) resulted in a 35.6% to 63.9% decrease in DNA repair synthesis, a 23.8% to 1347.6% increase in C2/C16 hydroxylation of E2, and a 53.8% to 72.4% decrease in anchorage-independent growth. The E2 metabolites at the highest non-cytotoxic doses of 0.76 µM estrone (E1), 0.69 µM 2-hydroxyestrone (2-OHE1), and 0.66 µM 2-methoxyestrone (2-MeOHE1) suppressed DMBA-induced DNA repair synthesis by 56.0% to 68.8%. These tumor suppressing agents and E2 metabolites also effectively suppressed post-initiational, anchorage-independent growth by 24.9% to 72.4%. These results indicate that DMBA induces cellular transformation in part by causing DNA damage, altering C2/C16 hydroxylation in favor of C16-hydroxylation, and inducing anchorage-independent growth prior to tumor development. Effective downregulation of these genotoxic, endocrine and proliferative end points by prototypic tumor suppressing agents and by E2 metabolites generated via the C2-hydroxylation pathway suggest that these agents may influence mammary tumorigenesis by inhibiting early occurring initiational and/or post initiational events.Abbreviations DMBA
7,12-dimethylbenz(a)anthracene
- HPR
N-(4-hydroxyphenyl) retinamide
- I3C
indole-3-carbinol
- TAM
tamoxifen
- E2
17-estradiol
- E1
estrone
- 2-OHE1
2-hydroxyestrone
- 2-MeOHE1
2-methoxyestrone
- 16-OHE1
16-hydroxyestrone
- E3
estriol
- DME/F12
Dulbecco's modified Eagle's medium
- F12
Ham's medium
- HU
hydroxyurea
- PBS
phosphate buffered saline
- NaOH
sodium hydroxide
- SDS
sodium dodecyl sulfate
- TCA
trichloroacetic acid
- [C2-3H] E2
estradiol labeled at C2 position
- [C16-3H] E2
estradiol labeled at C16 position
- ANOVA
analysis of variance 相似文献
30.
Molecular genetic studies of early breast cancer evolution 总被引:9,自引:0,他引:9
Peter O'Connell PhD Vladimir Pekkel PhD Suzanne Fuqua PhD C. Kent Osborne MD D. Craig Allred MD 《Breast cancer research and treatment》1994,32(1):5-12
Summary In the past few years there has been an explosion in the number of patients diagnosed with hyperplastic breast disease andin situ breast cancer. Based on epidemiological data, these morphologically defined lesions may be categorized as those with little malignant potential (e.g. typical hyperplasia or proliferative disease without atypia [PDWA]), those with significant malignant potential which may already be initiated (e.g. atypical ductal hyperplasia [ADH]), and early transformed lesions which are malignant but not yet invasive (e.g. ductal carcinomain situ [DCIS]). They may represent sequential evolutionary stages in the ontogeny of invasive breast cancer, with each morphologically defined stage resulting from accumulating genetic changes culminating in a transformed clonal lineage capable of invasion and metastasis. Using loss-of-heterozygosity (LOH) analysis, we are studying the genetic changes associated with these lesions in archival tissue samples. 50% (6/12) of the proliferative lesions (PDWA and ADH) and 80% of the DCIS shared their LOH patterns with more advanced lesions from the same breast, strongly supporting a precursor/product relationship between these lesions and the cancers they accompany. 相似文献