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21.
We compared the tumor-initiating activities toward mouse skin of two
structurally related polycyclic aromatic hydrocarbon diol epoxides: racemic
anti-1,2,3,4-tetrahydro-5,6-dimethylchrysene-1,2-diol-3,4- epoxide
(5,6-diMeCDE) and racemic anti-1,2,3,4-tetrahydro-5-
methylchrysene-1,2-diol-3,4-epoxide (5-MeCDE). Tumors induced by these diol
epoxides were analysed for mutations in the Ha-ras gene. 5,6- diMeCDE is
derived from the non-planar parent compound 5,6- dimethylchrysene, and
reacts to approximately equal extents with dA and dG in DNA, whereas
5-MeCDE is derived from a nearly planar parent compound, 5-methylchrysene,
and reacts mainly with dG in DNA. 5,6- diMeCDE, at initiating doses of 33,
100 or 400 nmol per mouse, induced 1.2, 2.2 and 6.2 skin tumors per mouse,
respectively. It was significantly less tumorigenic than 5-MeCDE which
induced 3.1, 7.5 and 9.1 skin tumors per mouse at the same doses. Tumors
induced by 5,6- diMeCDE had a large number of CAA-->CTA mutations in
codon 61 of the Ha- ras gene: 50, 55 and 75% of the tumors analysed had
this mutation at the 33, 100 and 400 nmol doses. No mutations were found in
codons 12 and 13 in the tumors induced by 5,6-diMeCDE. In contrast,
CAA-->CTA mutations in codon 61 were rarely seen in tumors induced by
5-MeCDE. At the highest dose of 5-MeCDE, 20% of the tumors analysed had
mutations at G of codons 12 and 13. The results of this comparative study
support the hypothesis that mutations in the Ha-ras gene in mouse skin
tumors induced by PAH diol epoxides occur as a result of their direct
reaction with the gene. However, pathways other than the commonly observed
Ha- ras codon 61 mutations are clearly important in mouse skin
tumorigenesis by these diol epoxides.
相似文献
22.
Véronique Duchêne Séverine Ferdinand Ingrid Filliol Jean Fran?ois Guégan Nalin Rastogi Christophe Sola 《Infection, genetics and evolution》2004,4(1):5-14
In order to compare phylogenetic methods and to reconstruct the evolutionary history of the tubercle bacilli, a set of macro-array-based genotyping data of Mycobacterium tuberculosis clinical isolates (called spoligotyping for spacer oligonucleotide typing, which assays the variability of the Direct Repeat -DR- locus), was analyzed in four settings of the Caribbean region (Guadeloupe, Martinique, Cuba and Haiti). A set of 47 alleles, split into 26 shared and 21 unique alleles) representative of 321 individual M. tuberculosis clinical isolates from patients residing in the above regions was studied. The following methods (and software in brackets) were investigated: numerical taxonomy distance methods (TAXOTRON), maximum parsimony procedure (PAUP), median-joining networks (NETWORK), and nested clade analysis (GEODIS). Results using these methods were analyzed, compared and discussed. The latter method (GEODIS) was investigated in detail by introducing geographical data together with genetic variability results to detect a link between population structure and population history, and to test the null hypothesis of no association between geography and genotypes. Irrespective of the methods used, our findings demonstrate that a core structure of four families (or clades) of M. tuberculosis strains is highly prevalent within the islands studied, indirectly reflecting passed colonization history of these different settings. Specificity of M. tuberculosis genotypes in each of the islands is discussed in the light of their respective colonial and contemporary histories. 相似文献
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Pinelli C D'Aniello B Sordino P Meyer DL Fiorentino M Rastogi RK 《Brain research. Developmental brain research》2000,119(2):195-208
The distribution of FMRFamide-like immunoreactive (ir) neurons and fibers was investigated in the central nervous system of developing zebrafish and juvenile sturgeon (sterlet). Adult zebrafish was also studied. In zebrafish embryos FMRFamide-ir elements first appeared 30 h post-fertilization (PF). Ir somata were located in the olfactory placode and in the ventral diencephalon. FMRFamide-ir fibers originating from diencephalic neurons were found in the ventral telencephalon and in ventral portions of the brainstem. At 48 h PF, the ir perikarya in the olfactory placode displayed increased immunoreactivity and stained fibers emerged from the somata. At 60 h PF, bilaterally, clusters of FMRFamide-ir neurons were found along the rostro-caudal axis of the brain, from the olfactory placode to rostral regions of the ventro-lateral telencephalon. At 60 h PF, numerous ir fibers appeared in the dorsal telencephalon, optic lobes, optic nerves, and retina. Except for ir fibers in the hypophysis at the age of 72 h PF, and a few ir cells in the nucleus olfacto-retinalis (NOR) at the age of 2 months PF, no major re-organization was noted in subsequent ontogenetic stages. The number of stained NOR neurons increased markedly in sexually mature zebrafish. In adult zebrafish, other ir neurons were located in the dorsal zones of the periventricular hypothalamus and in components of the nervus terminalis. We are inclined to believe that neurons expressing FMRFamide originate in the olfactory placode and in the ventricular ependyma in the hypothalamus. On the same grounds, a dual origin of FMRFamide-ir neurons is inferred in the sturgeon, an ancestral bony fish: prior to the observation of ir cells in the nasal area and in the telencephalon stained neurons were noted in circumventricular hypothalamic regions. 相似文献
25.
S S Sikora P Balachandran K Dimri N Rastogi A Kumar R Saxena V K Kapoor 《European journal of surgical oncology》2005,31(2):158-163
PURPOSE: Patterns of failure following surgical treatment of ampullary cancers indicate that up to 45% of patients develop loco-regional recurrence. The effect of adjuvant chemo-radiotherapy on survival and loco-regional control is not yet established in this malignancy. PATIENTS AND METHODS: From January 1989 to December 2000, 113 patients underwent pancreatico-duodenectomy for ampullary cancer. One hundred and four patients who survived the operation were available for analysis to study the effect of adjuvant chemo-radiotherapy on survival and loco-regional control. Forty-nine patients received adjuvant chemo-radiotherapy (median dose 50.4 Gy with concurrent 5-Flurouracil) and long-term outcome in these patients was compared with those 55 who did not receive adjuvant therapy. RESULTS: The overall median survival was 30.1 (range 1.6-140.0) months with actuarial 1, 3 and 5-year survival rates of 79, 43 and 33%, respectively. No significant difference in median survival (34.6 vs 24.5 months; P=0.3) and actuarial 5-year survival rates (38 vs 28%) was seen between those who received and those who did not receive adjuvant therapy. Adjuvant chemo-radiotherapy did not influence the survival in high-risk patients (P=0.84), in various T and N stages and had no impact on loco-regional recurrence (P=0.6). CONCLUSIONS: Adjuvant chemo-radiotherapy did not improve the long-term survival or decrease recurrence rates in patients with ampullary cancers who had undergone pancreatico-duodenectomy. 相似文献
26.
Elizabeth Tan-Chiu Greg Yothers Edward Romond Charles E Geyer Michael Ewer Deborah Keefe Richard P Shannon Sandra M Swain Ann Brown Louis Fehrenbacher Victor G Vogel Thomas E Seay Priya Rastogi Eleftherios P Mamounas Norman Wolmark John Bryant 《Journal of clinical oncology》2005,23(31):7811-7819
PURPOSE: Trastuzumab is effective in treating human epidermal growth factor receptor 2 (HER2) -positive breast cancer, but it increases frequency of cardiac dysfunction (CD) when used with or after anthracyclines. PATIENTS AND METHODS: National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide (AC) followed by paclitaxel with AC followed by paclitaxel plus 52 weeks of trastuzumab beginning concurrently with paclitaxel in patients with node-positive, HER2-positive breast cancer. Initiation of trastuzumab required normal post-AC left ventricular ejection fraction (LVEF) on multiple-gated acquisition scan. If symptoms suggestive of congestive heart failure (CHF) developed, source documents were blindly reviewed by an independent panel of cardiologists to determine whether criteria were met for a cardiac event (CE), which was defined as New York Heart Association class III or IV CHF or possible/probable cardiac death. Frequencies of CEs were compared between arms. RESULTS: Among patients with normal post-AC LVEF who began post-AC treatment, five of 814 control patients subsequently had confirmed CEs (four CHFs and one cardiac death) compared with 31 of 850 trastuzumab-treated patients (31 CHFs and no cardiac deaths). The difference in cumulative incidence at 3 years was 3.3% (4.1% for trastuzumab-treated patients minus 0.8% for control patients; 95% CI, 1.7% to 4.9%). Twenty-seven of the 31 patients in the trastuzumab arm have been followed for > or = 6 months after diagnosis of a CE; 26 were asymptomatic at last assessment, and 18 remained on cardiac medication. CHFs were more frequent in older patients and patients with marginal post-AC LVEF. Fourteen percent of patients discontinued trastuzumab because of asymptomatic decreases in LVEF; 4% discontinued trastuzumab because of symptomatic cardiotoxicity. CONCLUSION: Administering trastuzumab with paclitaxel after AC increases incidence of CHF and lesser CD. Potential cardiotoxicity should be carefully considered when discussing benefits and risks of this therapy. 相似文献
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本文用DSC和激光拉曼光谱研究抗癌药物足叶乙甙(4-去甲基表鬼臼毒素-β-D-乙叉吡喃葡萄糖甙,简称VP 16-213)与二棕榈酰磷脂酰胆碱(DPPC)脂质体的作用。VP 16-213分子掺入DPPC脂质体双层中,不但使相转变温度向高温移动,而且吸热峰的半高宽度随VP 16-213浓度增加而变宽。其Raman光谱在频率2850 cm~(-1)处的C-H键对称伸缩振动亦随着药物浓度增加而减弱。这些结果表明VP 16-213分子是定域在脂双层中DPPC分子链的C_1~C_9亚甲基区域,使脂质体的有序性提高而流动性降低。 相似文献
30.