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21.
G Slavin E J Wills J E Richmond I Chanarin T Andrews G Stewart 《Journal of clinical pathology》1975,28(9):701-710
The morphological changes in a patient with a generalized storage disease characterized by the intracellular deposition of neutral lipid are described. There is widespread accumulation of lipid in the cytoplasm of many cells and in occasional nuclei. Diagnosis may be facilitated by the recognition of clear vacuoles in the cytoplasm of granulocytes in blood films. In jejunal biopsies vacuolation of the epithelial cells may simulate the appearances of a-betalipoproteinaemia. The lipid inclusions consist largely of normal triglycerides and are free in the cytoplasm, unassociated with any organelle. The biochemical basis of the lesions is uncertain. Although there are lipoprotein abnormalities the primary defect appears to be intrinsic to the cell and may involve either a defective cytoplasmic lipase or an impaired uptake and utilization of fatty acids by mitochondria. 相似文献
22.
Gene conversion is a likely cause of mutation in PKD1 总被引:3,自引:0,他引:3
Watnick TJ; Gandolph MA; Weber H; Neumann HP; Germino GG 《Human molecular genetics》1998,7(8):1239-1243
Approximately 70% of the gene responsible for the most common form of
autosomal dominant polycystic kidney disease ( PKD1 ) is replicated in
several highly homologous copies located more proximally on chromosome 16.
We recently have described a novel technique for mutation detection in the
duplicated region of PKD1 that circumvents the difficulties posed by these
homologs. We have used this method to identify two patients with a nearly
identical cluster of base pair substitutions in exon 23. Since pseudogenes
are known to be reservoirs for mutation via gene conversion events for a
number of other diseases, we decided to test whether these sequence
differences in PKD1 could have arisen as a result of this mechanism. Using
changes in restriction digest patterns, we were able to show that these
sequence substitutions are also present in N23HA, a rodent-human somatic
cell hybrid that contains only the PKD1 homologs. Moreover, these changes
were also detected in total DNA from several affected and unaffected
individuals that did not harbor this mutation in their PKD1 gene copy. This
is the first example of gene conversion in PKD1 , and our findings
highlight the importance of using gene-specific reagents in defining PKD1
mutations.
相似文献
23.
Predominance of null mutations in ataxia-telangiectasia 总被引:15,自引:4,他引:15
Gilad S; Khosravi R; Shkedy D; Uziel T; Ziv Y; Savitsky K; Rotman G; Smith S; Chessa L; Jorgensen TJ; Harnik R; Frydman M; Sanal O; Portnoi S; Goldwicz Z; Jaspers NG; Gatti RA; Lenoir G; Lavin MF; Tatsumi K; Wegner RD; Shiloh Y; Bar-Shira A 《Human molecular genetics》1996,5(4):433-439
Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving
cerebellar degeneration, immunodeficiency, chromosomal instability,
radiosensitivity and cancer predisposition. The responsible gene, ATM, was
recently identified by positional cloning and found to encode a putative
350 kDa protein with a Pl 3-kinase-like domain, presumably involved in
mediating cell cycle arrest in response to radiation-induced DNA damage.
The nature and location of A-T mutations should provide insight into the
function of the ATM protein and the molecular basis of this pleiotropic
disease. Of 44 A-T mutations identified by us to date, 39 (89%) are
expected to inactivate the ATM protein by truncating it, by abolishing
correct initiation or termination of translation, or by deleting large
segments. Additional mutations are four smaller in-frame deletions and
insertions, and one substitution of a highly conserved amino acid at the Pl
3-kinase domain. The emerging profile of mutations causing A-T is thus
dominated by those expected to completely inactivate the ATM protein. ATM
mutations with milder effects may result in phenotypes related, but not
identical, to A-T.
相似文献
24.
25.
Electrical techniques were used to determine the NaK selectivity of the amiloride-sensitive pathway and to characterize cellular and paracellular properties of A6 epithelium. Under control conditions, the mean transepithelial voltage (V
T) was –57±5 mV, the short-circuit current (I
sc) averaged 23±2 A/cm2 and the transepithelial resistance (R
T) was 2.8±0.3 kcm2 (n=13). V
T and I
sc were larger than reported in previous studies and were increased by aldosterone. The conductance of the amiloride-sensitive pathway (G
amil) was assessed before and after replacement of Na+ in the mucosal bath by K+, using two independent measurements: (1) the slope conductance (G
T), determined from current-voltage (I-V) relationships for control and amiloride-treated tissues and (2) the maximum amiloride-sensitive conductance (G
max) calculated from the amiloride dose-response relationship. The ratio of G
amil in mucosal Na+ solutions to G
amil for mucosal K+ solutions was 22±6 for G
T measurements and 15±2 for G
max data. Serosal ion replacements in tissues treated with mucosal nystatin indicated a potassium conductance in the basolateral membrane. Equivalent circuit analyses of nystatin and amiloride data were used to resolve the cellular (E
c) and paracellular (R
j) resistances (5 kcm2 and 8–9 kcm2, respectively). Analysis I-V relationships for tissues depolarized with serosal K+ solutions revealed that the amiloride-sensitive pathway could be described as a Na+ conductance with a permeability coefficient (P
Na)=1.5±0.2× 10–6 cm/s and the intracellular Na+ concentration (Nai)=5±1 mM (n=5), similar to values from other tight epithelia. We conclude that A6 epithelia are capable of expressing large amiloride-sensitive currents which are highly Na+ selective. 相似文献
26.
Prostaglandin F and E levels during endotoxin-induced pulmonary hypertension in calves 总被引:10,自引:0,他引:10
Anderson FL; Tsagaris TJ; Jubiz W; Kuida H 《The American journal of physiology》1975,228(5):1479-1482
27.
28.
Arjan C.Y. Loenen David C. Noriega Carlos Ruiz Wills Jérôme Noailly Pierce D. Nunley Rainer Kirchner Keita Ito Bert van Rietbergen 《The spine journal》2021,21(3):528-537
BACKGROUND CONTEXTManual contouring of spinal rods is often required intraoperatively for proper alignment of the rods within the pedicle screw heads. Residual misalignments are frequently reduced by using dedicated reduction devices. The forces exerted by these devices, however, are uncontrolled and may lead to excessive reaction forces. As a consequence, screw pullout might be provoked and surrounding tissue may experience unfavorable biomechanical loads. The corresponding loads and induced tissue deformations are however not well identified. Additionally, whether the forced reduction alters the biomechanical behavior of the lumbar spine during physiological movements postoperatively, remains unexplored.PURPOSETo predict whether the reduction of misaligned posterior instrumentation might result in clinical complications directly after reduction and during a subsequent physiological flexion movement.STUDY DESIGNFinite element analysis.METHODSA patient-specific, total lumbar (L1–S1) spine finite element model was available from previous research. The model consists of poro-elastic intervertebral discs with Pfirrmann grade-dependent material parameters, with linear elastic bone tissue with stiffness values related to the local bone density, and with the seven major ligaments per spinal motion segment described as nonlinear materials. Titanium instrumentation was implemented in this model to simulate a L4, L5, and S1 posterolateral fusion. Next, coronal and sagittal misalignments of 6 mm each were introduced between the rod and the screw head at L4. These misalignments were computationally reduced and a physiological flexion movement of 15° was prescribed. Non-instrumented and well-aligned instrumented models were used as control groups.RESULTSPulling forces up to 1.0 kN were required to correct the induced misalignments of 6 mm. These forces affected the posture of the total lumbar spine, as motion segments were predicted to rotate up to 3 degrees and rotations propagated proximally to and even affect the L1–2 level. The facet contact pressures in the corrected misaligned models were asymmetrical suggesting non-physiological joint loading in the misaligned models. In addition, the discs and vertebrae experienced abnormally high forces as a result of the correction procedure. These effects were more pronounced after a 15° flexion movement following forced reduction.CONCLUSIONSThe results of this study indicate that the correction of misaligned posterior instrumentation can result in high forces at the screws consistent with those reported to cause screw pullout, and may cause high-tissue strains in adjacent and downstream spinal segments.CLINICAL SIGNIFICANCEProper alignment of spinal posterior instrumentation may reduce clinical complications secondary to unfavorable biomechanics. 相似文献
29.
Brat DJ Wills ML Lecksell KL Epstein JI 《The American journal of surgical pathology》1999,23(3):257-262
The authors determined whether clinically relevant diagnostic information would be lost by examination of <3 levels per tissue core in prostate needle biopsy specimens. They evaluated 439 consecutive sextant biopsy specimens for the following three histopathologic features: presence of adenocarcinoma involving one core, Gleason pattern 4 in cases of grade 3 + 4 = 7 adenocarcinoma, and perineural invasion (PNI) by carcinoma. For all cases, 3 levels from each involved core were reviewed for the presence or absence of these three features. In 50 cases with adenocarcinoma involving only 1 core, diagnostic carcinoma was present on all 3 levels in 43 cores (86%). Carcinoma was present on only 2 levels in 3 cores (6%), present only on 1 level in 3 cores (6%), and present only on additional cut-downs, not on the original 3 levels in 1 core (2%). Among 32 cases, 51 cores were identified that contained Gleason grade 3 + 4 = 7 adenocarcinoma. In 41 cores (80%), pattern 4 was identified in all 3 levels. In 5 cores (10%), pattern 4 was identified on only 2 levels, and in another 5 cores (10%), pattern 4 was present on only 1 level. Among 36 cases, 69 tissue cores were identified that contained perineural invasion (PNI). In 54 cores (78%), PNI was present on all 3 levels. In 7 cores (10%), PNI was present on only 2 of 3 levels, while in 7 other cores (10%), PNI was present on only 1 of 3 levels. In 1 core (1.5%), PNI was noted only on additional cutdowns, not on the original 3 levels. We estimated that reducing the number of levels to 1 per core could result in the misdiagnosis of PNI, grading, or carcinoma in approximately 8-11% of cores with these features and could have changed the case diagnosis in 9 of 439 cases. If only 2 levels were reviewed, we predict misdiagnosis in 5% to 6% of cores with these features and a change in the case diagnosis in 5 of 439 cases. Misdiagnosis of clinically relevant features on prostate biopsy specimens can be minimized with histologic review of 3 levels per tissue core. 相似文献
30.
We report a case of a parturient with documented chronic Chagas' disease with cardiac manifestations presenting for labor management and complicated by the need for emergent hysterectomy after delivery. Chagas' disease is a common human hematogenous trypanosomiasis in Central and South America which is now, because of population migration, appearing in the USA. This disease predominantly affects the heart and the gastrointestinal system. This report discusses the parasite, the acute and chronic phases of Chagas' disease and highlights its medical implications, including maternal-fetal transfer of Trypanosoma cruzi. 相似文献