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101.
Michelle E Kruijshaar Marie-Louise Essink-Bot Bas Donkers Caspar WN Looman Peter D Siersema Ewout W Steyerberg 《BMC medical research methodology》2009,9(1):31
Background
Discrete choice experiments (DCEs) allow systematic assessment of preferences by asking respondents to choose between scenarios. We conducted a labelled discrete choice experiment with realistic choices to investigate patients' trade-offs between the expected health gains and the burden of testing in surveillance of Barrett esophagus (BE). 相似文献102.
103.
Increased tumors but uncompromised fertility in the female descendants of mice exposed developmentally to diethylstilbestrol 总被引:11,自引:1,他引:10
Newbold RR; Hanson RB; Jefferson WN; Bullock BC; Haseman J; McLachlan JA 《Carcinogenesis》1998,19(9):1655-1663
Prenatal exposure to diethylstilbestrol (DES) has been associated with the
subsequent development of reproductive tract abnormalities, including poor
reproductive outcome and neoplasia, in experimental animals and humans.
Experimental animal studies with chemical carcinogens have raised the
possibility that adverse effects of DES may be transmitted to succeeding
generations. To evaluate this possibility and to determine if there is a
sensitive window of developmental exposure, outbred CD-1 mice were treated
with DES during three stages of development: group 1 was treated on days
9-16 of gestation (2.5, 5 or 10 microg/kg maternal body wt), the time of
major organogenesis; group II was treated once on day 18 of gestation (1000
microg/kg maternal body wt) just prior to birth; group III was treated on
days 1- 5 of neonatal life (0.002 microg/pup/day). Female mice (F1) in each
group were raised to sexual maturity and bred to control males. As
previously reported, fertility of the F1 DES-exposed females was decreased
in all groups. Female offspring (DES lineage or F2) from these matings were
raised to maturity and housed with control males for 20 weeks. The
fertility of these DES lineage female mice was not affected by DES exposure
of their 'grandmothers'. DES lineage mice were killed at 17-19 and 22-24
months of age. An increased incidence of malignant reproductive tract
tumors, including uterine adenocarcinoma, was seen in DES lineage mice but
not in corresponding controls; the range and prevalence of tumors increased
with age. Because uterine adenocarcinomas were seen in all three DES
groups, all developmental exposure periods were considered susceptible to
the adverse effects of DES. These data suggest that the reduced fertility
observed in the DES F1 female mice was not transmitted to their
descendants; however, increased susceptibility to tumor formation is
apparently transmitted to subsequent generations.
相似文献
104.
We attempted to use hand-held, high-resolution breast sonography to localize for biopsy 11 solid, nonpalpable lesions detected by mammography. Using sonography, we identified and localized only one of four lesions presenting as poorly defined masses and only one of seven lesions presenting as clusters of tiny calcifications. This 18% rate of success is too low to justify the use of sonography for all patients undergoing needle localization. Mammography remains the procedure of choice for localizing solid, nonpalpable breast masses and clustered calcifications. 相似文献
105.
van Veen EB Riegman PH Dinjens WN Lam KH Oomen MH Spatz A Mager R Ratcliffe C Knox K Kerr D van Damme B van de Vijver M van Boven H Morente MM Alonso S Kerjaschki D Pammer J Lopez-Guerrero JA Llombart Bosch A Carbone A Gloghini A Teodorovic I Isabelle M Passioukov A Lejeune S Therasse P Oosterhuis JW 《European journal of cancer (Oxford, England : 1990)》2006,42(17):2914-2923
The regulatory regimes for research with residual tissue and accompanying data differ widely between countries in the European Union (EU): from specific consent to opt-out or even no consent at all. This could greatly hamper research where the exchange of tissue and accompanying data has become the gold standard, like in TubaFrost. Instead of adhering to international guidelines, which have a democratic deficit, or an attempt for a new set of possible harmonising rules, TubaFrost chose to create a coordinating rule: if tissue may legitimately be used for a certain kind of research in the country where it was taken and under whose jurisdiction the patient falls, it may also be used for such research in the country where it is sent to in the context of a scientific program even if in that other country other regulations would apply for research with residual tissue taken from patients under their jurisdiction. This coordinating rule has a sound basis in EU law in general and will solve the problems related to diverging national regulatory regimes in the case of cross national research with residual tissue. 相似文献
106.
Jolanda M van Dieren Josiane C Wink Kees J Vissers Ronald van Marion Monique M C P Hoogmans Winand N M Dinjens W Ruud Schouten Hans J Tanke Karoly Szuhai Ernst J Kuipers C Janneke van der Woude Herman van Dekken 《Diagnostic molecular pathology》2006,15(4):216-222
Longstanding ulcerative colitis (UC) is associated with a high risk of developing UC-related colonic adenocarcinoma (UCC). These carcinomas originate from nonadenomatous dysplastic regions referred to as dysplasia associated lesion or mass (DALM). We evaluated chromosomal and microsatellite instability (MSI) in 21 DALM/UCCs. Chromosomal instability was determined by high-resolution array comparative genomic hybridization with a 3500-element BAC-PAC array. MSI was assessed with markers BAT25 and BAT26 and by immunohistochemical analysis of mismatch repair genes. Comparative genomic hybridization revealed frequent losses of array clones (>20% of tumors) at chromosome arms 4p, 5q, and 18q, frequent gains of array clones (>20% of tumors) were found at 1q, 5p, 6p, 7p, 7q, 8p, 8q, 11p, 11q, 12q, 14q, 17q, 19q, 20p, and 20q. The pattern of alterations is dominated by gains on 5p and 20q with loss of 4p, all of which were already present in a patient with carcinoma in situ. Immunohistochemical analysis of mismatch repair genes MLH1, PMS2, MSH2, and MSH6 showed negative immunostaining in 1 neoplasm (5%). MSI of BAT25 and BAT26 was seen in 3 tumors (14%) including the neoplasm with aberrant immunostaining. In conclusion, we constructed a genomic profile of DALM/UCC including several novel genetic alterations. Further, we found a low percentage of MSI. Thus, DALM/UCCs display profound chromosomal instability, but this is not associated with concurrent MSI. 相似文献
107.
108.
Microsatellite instability in a pleomorphic rhabdomyosarcoma in a patient with hereditary non-polyposis colorectal cancer 总被引:3,自引:0,他引:3
AIMS: To describe the rare occurrence of a pleomorphic sarcoma with microsatellite instability in a patient with hereditary non-polyposis colorectal cancer (HNPCC). METHODS AND RESULTS: A soft tissue tumour was removed from the upper leg of a patient who had previously been shown to harbour a germ-line MSH-2 mutation. The tumour was analysed with immunohistochemistry and molecular methods. The morphology and immunohistochemical findings were in keeping with a pleomorphic rhabdomyosarcoma. Microsatellite instability was documented in the tumour with molecular methods and in addition loss of MSH-2 expression in the tumour cells was confirmed by immunohistochemistry. CONCLUSIONS: Although sarcomas do not form part of the HNPCC diagnostic criteria, they may occur in this mismatch repair syndrome and, moreover, may well be caused by the underlying genetic defect. 相似文献
109.
Khan WN; Nilsson A; Mizoguchi E; Castigli E; Forsell J; Bhan AK; Geha R; Sideras P; Alt FW 《International immunology》1997,9(3):395-405
Mutations in Bruton's tyrosine kinase (Btk) gene, in mice, result in
reduced numbers and responses of peripheral B cells. Surface Ig- mediated
signaling is defective in Btk mutant B cells as they do not proliferate
upon slg cross-linking and lack thymus-independent (TI) type II responses.
Signals through sIg and CD40 play a critical role in B cell maturation. To
investigate the consequences of the lack of both Btk and CD40 on B cell
development and function, mice were generated that were homozygous for
targeted mutations in the Btk and the CD40 genes (BtkMCD40M). The CD40
mutation (CD40M) had a synergistic effect on the BtkM defects. In BtkMCD40M
mice the number of B cells was reduced 3- to 4-fold compared to BtkM mice
and mature B cells (IgMlow/IgDhigh) were virtually absent; serum levels of
all Ig isotypes were diminished; and antibody responses to TI-I TI-II and
thymus- dependent antigens were impaired. Furthermore, although wild-type
BtkM and CD40M mice produced germinal centers in response to TI-I antigen,
the BtkMCD40M mice did not. Maturational and functional B cell defects in
BtkMCD40M mice may result from a combination of intrinsic B cell defects,
lack of CD40L-dependent T cell help and microenvironmental defects. These
data suggest that signals through Btk and CD40 are necessary for the
production and maintenance of the mature B cell.
相似文献
110.
AMP deaminase as a cell-age marker in transient erythroblastopenia of childhood and its role in the adenylate economy of erythrocytes 总被引:1,自引:0,他引:1
Erythrocytes from 11 patients with presumptive diagnoses of transient erythroblastopenia of childhood were evaluated retrospectively (six) or prospectively (five) for a possible relationship between erythrocyte adenosine 5'-monophosphate aminohydrolase, adenylic acid deaminase (AMP deaminase) activity and intracellular concentrations of adenine nucleotides. Older red blood cell (RBC) cohorts in these patients consistently exhibited significantly decreased activities of AMP deaminase (approximately 5% to 70% of normal control mean) in association with increased concentrations (up to threefold) of adenosine triphosphate (ATP) and total adenine nucleotides. We postulate that the latter is a direct consequence of the former, since diminishing AMP deaminase activity in aging cells should reduce the drain on the adenine nucleotide pool imposed by irreversible deamination of AMP to inosine 5'-monophosphate. Consistent reductions in AMP deaminase activity indicate that this enzyme should also serve as a reliable marker of mean RBC age useful in diagnostic confirmation of transient erythroblastopenia. The observed increases in ATP and total adenine nucleotides in older RBCs require a reevaluation of the traditional view that age-related losses of these compounds mediate the ultimate demise of senescent erythrocytes. Similar alterations in the balance of degradative and salvage pathways in RBC nucleotide metabolism may also underlie certain cases of so-called "high ATP syndrome." 相似文献